Arterial baroreceptors mediate the inhibitory effect of acute increases in arterial blood pressure on thirst

The present study sought to determine whether arterial baroreceptor afferents mediate the inhibitory effect of an acute increase in arterial blood pressure (AP) on thirst stimulated by systemically administered ANG II or by hyperosmolality. Approximately 2 wk after sinoaortic denervation, one of four doses of ANG II (10, 40, 100, or 250 ng. kg(-1) x min(-1)) was infused intravenously in control and complete sinoaortic-denervated (SAD) rats. Complete SAD rats ingested more water than control rats when infused with 40, 100, or 250 ng x kg(-1) x min(-1) ANG II. Furthermore, complete SAD rats displayed significantly shorter latencies to drink compared with control rats. In a separate group of rats, drinking behavior was stimulated by increases in plasma osmolality, and mean AP was raised by an infusion of phenylephrine (PE). The infusion of PE significantly reduced water intake and lengthened the latencies to drink in control rats but not in complete SAD rats. In all experiments, drinking behavior of rats that were subjected to sinoaortic denervation surgery but had residual baroreceptor reflex function (partial SAD rats) was similar to that of control rats. Thus it appears that arterial baroreceptor afferents mediate the inhibitory effect of an acute increase in AP on thirst stimulated by ANG II or hyperosmolality.     

Impairment of sympathetic baroreceptor reflexes in obese Zucker rats

Adult obese Zucker rats (OZRs) have elevated sympathetic vasomotor tone and arterial pressure (AP) with blunted baroreflex-mediated changes in heart rate (HR) compared with adult lean Zucker rats (LZRs). The present study examined whether compromised cardiac baroreflexes are indicative of attenuated sympathetic responses. In addition, because juvenile OZRs have a normal mean AP, we determined whether baroreflexes are fully functional prior to hypertension. At 13 wk, adult OZRs had an elevated baseline mean AP compared with LZRs (137 +/- 3 vs. 123 +/- 5 mmHg, P < 0.05) under urethane anesthesia. Phenylephrine-induced increases in AP evoked smaller inhibitions of splanchnic sympathetic nerve activity (SNA) and HR in OZRs compared with LZRs. In addition, sympathoexcitatory responses to nitroprusside-induced hypotension were also blunted in OZRs. Sigmoid analysis revealed a decreased gain, a higher mean AP at the midpoint of the curve (AP(50)), and a reduced range of changes in SNA in OZRs. In contrast, at 7 wk of age, although juvenile OZRs weighed more than LZRs (313 +/- 13 vs. 204 +/- 4 g, P < 0.05), mean AP was comparable in both groups (122 +/- 5 vs. 121 +/- 4 mmHg, not significant). In these rats, rapid changes in AP evoked comparable changes in SNA and HR in OZRs and LZRs. Sigmoid analysis revealed that, although the gain of the reflex was blunted in OZRs (P < 0.05), the mean AP(50) and range of changes in SNA were comparable in OZRs and LZRs. Together, these data indicate that in adult OZRs, sympathetic responses to acute changes in AP are smaller than those observed in adult LZRs and that impairment of baroreceptor reflexes in OZR is not limited to the regulation of HR but extends to sympathetic vasomotor control. In addition, most of these deficits in baroreflex control of SNA develop in adulthood long after the onset of obesity and when other deficits in cardiovascular regulation are present.     

Chronic angiotensin II infusion attenuates the renal sympathoinhibitory response to acute volume expansion

In this study the hypothesis was tested that chronic infusion of ANG II attenuates acute volume expansion (VE)-induced inhibition of renal sympathetic nerve activity (SNA). Rats received intravenous infusion of either vehicle or ANG II (12 ng. kg(-1). min(-1)) for 7 days. ANG II-infused animals displayed an increased contribution of SNA to the maintenance of mean arterial pressure (MAP) as indicated by ganglionic blockade, which produced a significantly (P < 0.01) greater decrease in MAP (75 +/- 3 mmHg) than was observed in vehicle-infused (47 +/- 8 mmHg) controls. Rats were then anesthetized, and changes in MAP, mean right atrial pressure (MRAP), heart rate (HR), and renal SNA were recorded in response to right atrial infusion of isotonic saline (20% estimated blood volume in 5 min). Baseline MAP, HR, and hematocrit were not different between groups. Likewise, MAP was unchanged by acute VE in vehicle-infused animals, whereas VE induced a significant bradycardia (P < 0.05) and increase in MRAP (P < 0.05). MAP, MRAP, and HR responses to VE were not statistically different between animals infused with vehicle vs. ANG II. In contrast, VE significantly (P < 0.001) reduced renal SNA by 33.5 +/- 8% in vehicle-infused animals but was without effect on renal SNA in those infused chronically with ANG II. Acutely administered losartan (3 mg/kg iv) restored VE-induced inhibition of renal SNA (P < 0.001) in rats chronically infused with ANG II. In contrast, this treatment had no effect in the vehicle-infused group. Therefore, it appears that chronic infusion of ANG II can attenuate VE-induced renal sympathoinhibition through a mechanism requiring AT(1) receptor activation. The attenuated sympathoinhibitory response to VE in ANG II-infused animals remained after arterial barodenervation and systemic vasopressin V(1) receptor antagonism and appeared to depend on ANG II being chronically increased because ANG II given acutely had no effect on VE-induced renal sympathoinhibition.     

Baroreceptor reflex modulation by circulating angiotensin II is mediated by AT1 receptors in the nucleus tractus solitarius

Circulating ANG II modulates the baroreceptor reflex control of heart rate (HR), at least partly via activation of ANG II type 1 (AT1) receptors on neurons in the area postrema. In this study, we tested the hypothesis that the effects of circulating ANG II on the baroreflex also depend on AT1 receptors within the nucleus tractus solitarius (NTS). In confirmation of previous studies in other species, increases in arterial pressure induced by intravenous infusion of ANG II had little effect on HR in urethane-anesthetized rats, in contrast to the marked bradycardia evoked by equipressor infusion of phenylephrine. In the presence of a continuous background infusion of ANG II, the baroreflex control of HR was shifted to higher levels of HR but had little effect on the baroreflex control of renal sympathetic activity. The modulatory effects of circulating ANG II on the cardiac baroreflex were significantly reduced by microinjection of candesartan, an AT1 receptor antagonist, into the area postrema and virtually abolished by microinjections of candesartan into the medial NTS. After acute ablation of the area postrema, a background infusion of ANG II still caused an upward shift of the cardiac baroreflex curve, which was reversed by subsequent microinjection of candesartan into the medial NTS. The results indicate that AT1 receptors in the medial NTS play a critical role in modulation of the cardiac baroreflex by circulating ANG II via mechanisms that are at least partly independent of AT1 receptors in the area postrema.     

Central mechanisms of acute ANG II modulation of arterial baroreflex control of renal sympathetic nerve activity

Short-term intravenous infusion of angiotensin II (ANG II) into conscious rabbits reduces the range of renal sympathetic nerve activity (RSNA) by attenuating reflex disinhibition of RSNA. This action of ANG II to attenuate the arterial baroreflex range is exaggerated when ANG II is directed into the vertebral circulation, which suggests a mechanism involving the central nervous system. Because an intact area postrema (AP) is required for ANG II to attenuate arterial baroreflex-mediated bradycardia and is also required for maintenance of ANG II-dependent hypertension, we hypothesized that attenuation of maximum RSNA during infusion of ANG II involves the AP. In conscious AP-lesioned (APX) and AP-intact rabbits, we compared the effect of a 5-min intravenous infusion of ANG II (10 and 20 ng x kg(-1) x min(-1)) on the relationship between mean arterial blood pressure (MAP) and RSNA. Intravenous infusion of ANG II into AP-intact rabbits resulted in a dose-related attenuation of maximum RSNA observed at low MAP. In contrast, ANG II had no effect on maximum RSNA in APX rabbits. To further localize the central site of ANG II action, its effect on the arterial baroreflex was assessed after a midcollicular decerebration. Decerebration did not alter arterial baroreflex control of RSNA compared with the control state, but as in APX, ANG II did not attenuate the maximum RSNA observed at low MAP. The results of this study indicate that central actions of peripheral ANG II to attenuate reflex disinhibition of RSNA not only involve the AP, but may also involve a neural interaction rostral to the level of decerebration.     

Enhanced angiotensin II-mediated central sympathoexcitation in streptozotocin-induced diabetes: role of superoxide anion

Studies have shown that the superoxide mechanism is involved in angiotensin II (ANG II) signaling in the central nervous system. We hypothesized that ANG II activates sympathetic outflow by stimulation of superoxide anion in the paraventricular nucleus (PVN) of streptozotocin (STZ)-induced diabetic rats. In α-chloralose- and urethane-anesthetized rats, microinjection of ANG II into the PVN (50, 100, and 200 pmol) produced dose-dependent increases in renal sympathetic nerve activity (RSNA), arterial pressure (AP), and heart rate (HR) in control and STZ-induced diabetic rats. There was a potentiation of the increase in RSNA (35.0 ± 5.0 vs. 23.0 ± 4.3%, P < 0.05), AP, and HR due to ANG II type I (AT(1)) receptor activation in diabetic rats compared with control rats. Blocking endogenous AT(1) receptors within the PVN with AT(1) receptor antagonist losartan produced significantly greater decreases in RSNA, AP, and HR in diabetic rats compared with control rats. Concomitantly, there were significant increases in mRNA and protein expression of AT(1) receptor with increased superoxide levels and expression of NAD(P)H oxidase subunits p22(phox), p47(phox), and p67(phox) in the PVN of rats with diabetes. Pretreatment with losartan (10 mg·kg(-1)·day(-1) in drinking water for 3 wk) significantly reduced protein expression of NAD(P)H oxidase subunits (p22(phox) and p47(phox)) in the PVN of diabetic rats. Pretreatment with adenoviral vector-mediated overexpression of human cytoplasmic superoxide dismutase (AdCuZnSOD) within the PVN attenuated the increased central responses to ANG II in diabetes (RSNA: 20.4 ± 0.7 vs. 27.7 ± 2.1%, n = 6, P < 0.05). These data support the concept that superoxide anion contributes to an enhanced ANG II-mediated signaling in the PVN involved with the exaggerated sympathoexcitation in diabetes.     

Angiotensin-mediated increase in renal sympathetic nerve discharge within the PVN: role of nitric oxide

The paraventricular nucleus (PVN) of the hypothalamus is known to be an important site of integration in the central nervous system for sympathetic outflow. ANG II and nitric oxide (NO) play an important role in regulation of sympathetic nerve activity. The purpose of the present study was to examine how the interaction between NO and ANG II within the PVN affects sympathetic outflow in rats. Renal sympathetic nerve discharge (RSND), arterial blood pressure (AP), and heart rate (HR) were measured in response to administration of ANG II and N(G)-monomethyl-l-arginine (L-NMMA) into the PVN. Microinjection of ANG II (0.05, 0.5, and 1.0 nmol) into the PVN increased RSND, AP, and HR in a dose-dependent manner, resulting in increases of 53 +/- 9%, 19 +/- 3 mmHg, and 32 +/- 12 beats/min from baseline, respectively, at the highest dose. These responses were significantly enhanced by prior microinjection of L-NMMA and were blocked by losartan, an ANG II type 1 receptor antagonist. Similarly, administration of antisense to neuronal NO synthase within the PVN also potentiated the ANG II responses. Conversely, overexpression of neuronal NOS within the PVN with adenoviral gene transfer significantly attenuated ANG II responses. Push-pull administration of ANG II (1 nmol) into the PVN induced an increase in NO release. Our data indicate that ANG II type 1 receptors within the PVN mediate an excitatory effect on RSND, AP, and HR. NO in the PVN, which can be induced by ANG II stimulation, in turn inhibits the ANG II-mediated increase in sympathetic nerve activity. This negative-feedback mechanism within the PVN may play an important role in maintaining the overall balance and tone of sympathetic outflow.     

Norepinephrine reuptake, baroreflex dynamics, and arterial pressure variability in rats

This study examined the effect of norepinephrine reuptake blockade with desipramine (DMI) on the spontaneous variability of the simultaneously recorded arterial pressure (AP) and renal sympathetic nerve activity (SNA) in conscious rats. Acute DMI administration (2 mg/kg iv) depressed AP Mayer waves ( approximately 0.4 Hz) and increased low-frequency (<0.2 Hz) components of AP variability. DMI decreased renal SNA variability, especially due to the abolition of oscillations related to Mayer waves. To examine whether DMI-induced changes in AP and renal SNA variabilities could be explained by alterations in the dynamic characteristics of the baroreceptor reflex loop, the frequency responses of mean AP to aortic depressor nerve stimulation were studied in urethan-anesthetized rats. DMI accentuated the low-pass filter properties of the transfer function without significantly altering the fixed time delay. The frequency responses of iliac vascular conductance to stimulation of the lumbar sympathetic chain were studied in an additional group of anesthetized rats. DMI did not markedly alter the low-pass filter properties of the transfer function and slightly increased the fixed time delay. These results suggest that the DMI-induced decrease in the dynamic gain of the baroreceptor reflex is responsible for the decreased spontaneous renal SNA variability and the accompanying increased AP variability. The "slowing down" of baroreflex responses cannot be attributed to an effect of DMI at the vascular neuroeffector junction.     

Effect of Barodenervation on Cardiovascular Responses Elicited from the Hypothalamic Arcuate Nucleus of the Rat

We have previously reported that chemical stimulation of the hypothalamic arcuate nucleus (ARCN) in the rat elicited increases as well as decreases in blood pressure (BP) and sympathetic nerve activity (SNA). The type of response elicited from the ARCN (i.e., increase or decrease in BP and SNA) depended on the level of baroreceptor activity which, in turn, was determined by baseline BP in rats with intact baroreceptors. Based on this information, it was hypothesized that baroreceptor unloading may play a role in the type of response elicited from the ARCN. Therefore, the effect of barodenervation on the ARCN-induced cardiovascular and sympathetic responses and the neurotransmitters in the hypothalamic paraventricular nucleus (PVN) mediating the excitatory responses elicited from the ARCN were investigated in urethane-anesthetized adult male Wistar rats. Bilateral barodenervation converted decreases in mean arterial pressure (MAP) and greater splanchnic nerve activity (GSNA) elicited by chemical stimulation of the ARCN with microinjections of N-methyl-D-aspartic acid to increases in MAP and GSNA and exaggerated the increases in heart rate (HR). Combined microinjections of NBQX and D-AP7 (ionotropic glutamate receptor antagonists) into the PVN in barodenervated rats converted increases in MAP and GSNA elicited by the ARCN stimulation to decreases in MAP and GSNA and attenuated increases in HR. Microinjections of SHU9119 (a melanocortin 3/4 receptor antagonist) into the PVN in barodenervated rats attenuated increases in MAP, GSNA and HR elicited by the ARCN stimulation. ARCN neurons projecting to the PVN were immunoreactive for proopiomelanocortin, alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH). It was concluded that increases in MAP and GSNA and exaggeration of tachycardia elicited by the ARCN stimulation in barodenervated rats may be mediated via release of alpha-MSH and/or ACTH and glutamate from the ARCN neurons projecting to the PVN.     

Glutamatergic inputs to the CVLM independent of the NTS promote tonic inhibition of sympathetic vasomotor tone in rats

GABAergic neurons in the caudal ventrolateral medulla (CVLM) are driven by baroreceptor inputs relayed via the nucleus tractus solitarius (NTS), and they inhibit neurons in rostral ventrolateral medulla to reduce sympathetic nerve activity (SNA) and arterial pressure (AP). After arterial baroreceptor denervation or lesions of the NTS, inhibition of the CVLM continues to increase AP, suggesting additional inputs also tonically activate the CVLM. This study examined whether the NTS contributes to baroreceptor-independent drive to the CVLM and whether glutamate promotes baroreceptor- and NTS-independent activation of the CVLM to tonically reduce SNA. In addition, we evaluated whether altering central respiratory drive, a baroreceptor-independent regulator of CVLM neurons, influences glutamatergic inputs to the CVLM. Splanchnic SNA and AP were measured in chloralose-anesthetized, ventilated, paralyzed rats. The infusion of nitroprusside decreased AP below threshold for baroreceptor afferent firing (<50 mmHg) and increased SNA to 209+/-22% (P<0.05), but the subsequent inhibition of the NTS by microinjection of the GABA(A) agonist muscimol did not further increase SNA. In contrast, after inhibition of the NTS, blockade of glutamatergic inputs to CVLM by microinjection of kynurenate increased SNA (274+/-54%; P<0.05; n=7). In vagotomized rats with baroreceptors unloaded, inhibition of glutamatergic inputs to CVLM evoked a larger rise in SNA when central respiratory drive was increased (219+/-16% vs. 271+/-17%; n=5; P<0.05). These data suggest that baroreceptor inputs provide the major drive for the NTS-mediated excitation of the CVLM. Furthermore, glutamate tonically activates the CVLM to reduce SNA independent of the NTS, and this excitatory input appears to be affected by the strength of central respiratory drive.     

Angiotensin II acutely attenuates range of arterial baroreflex control of renal sympathetic nerve activity

Acutely increasing peripheral angiotensin II (ANG II) reduces the maximum renal sympathetic nerve activity (RSNA) observed at low mean arterial blood pressures (MAPs). We postulated that this observation could be explained by the action of ANG II to acutely increase arterial blood pressure or increase circulating arginine vasopressin (AVP). Sustained increases in MAP and increases in circulating AVP have previously been shown to attenuate maximum RSNA at low MAP. In conscious rabbits pretreated with an AVP V1 receptor antagonist, we compared the effect of a 5-min intravenous infusion of ANG II (10 and 20 ng x kg(-1) x min(-1)) on the relationship between MAP and RSNA when the acute pressor action of ANG II was left unopposed with that when the acute pressor action of ANG II was opposed by a simultaneous infusion of sodium nitroprusside (SNP). Intravenous infusion of ANG II resulted in a dose-related attenuation of the maximum RSNA observed at low MAP. When the acute pressor action of ANG II was prevented by SNP, maximum RSNA at low MAP was attenuated, similar to that observed when ANG II acutely increased MAP. In contrast, intravertebral infusion of ANG II attenuated maximum RSNA at low MAP significantly more than when administered intravenously. The results of this study suggest that ANG II may act within the central nervous system to acutely attenuate the maximum RSNA observed at low MAP.     

Microinjection of ANG II into paraventricular nucleus enhances cardiac sympathetic afferent reflex in rats

The aims of present study were to determine whether angiotensin II (ANG II) in the paraventricular nucleus (PVN) is involved in the central integration of the cardiac sympathetic afferent reflex and whether this effect is mediated by the ANG type 1 (AT(1)) receptor. While the animals were under alpha-chloralose and urethane anesthesia, mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) were recorded in sinoaortic-denervated and cervical-vagotomized rats. A cannula was inserted into the left PVN for microinjection of ANG II. The cardiac sympathetic afferent reflex was tested by electrical stimulation (5, 10, 20, and 30 Hz in 10 V and 1 ms) of the afferent cardiac sympathetic nerves or epicardial application of bradykinin (BK) (0.04 and 0.4 microg in 2 microl). Microinjection of ANG II (0.03, 0.3, and 3 nmol) into the PVN resulted in dose-related increases in the RSNA responses to electrical stimulation. The percent change of RSNA response to 20- and 30-Hz stimulation increased significantly at the highest dose of ANG II (3 nmol). The effects of ANG II were prevented by pretreatment with losartan (50 nmol) into the PVN. Microinjection of ANG II (0.3 nmol) into the PVN significantly enhanced the RSNA responses to epicardial application of BK, which was abolished by pretreatment with losartan (50 nmol) into the PVN. These results suggest that exogenous ANG II in the PVN augments the cardiac sympathetic afferent reflex evoked by both electrical stimulation of cardiac sympathetic afferent nerves and epicardial application of BK. These central effects of ANG II are mediated by AT(1) receptors.     

Brain stem control of arterial pressure in chronic arterial baroreceptor-denervated rats

Interruption of the baroreceptor reflex by transection of afferent nerves (sinoaortic denervation; SAD) or lesions of nucleus tractus solitarius (NTS) elevates sympathetic nerve activity (SNA) and arterial pressure (AP). However, within 1 wk, mean AP returns to normal despite the absence of baroreflexes. In this study, we examine central mechanisms that control AP in chronic baroreceptor-denervated rats. In urethane-anesthetized rats (1.5 g/kg i.v.) after autonomic ganglionic blockade (5 mg/kg i.v. chlorisondamine), alpha1-adrenergic-mediated pressor responses (1-100 microg/kg i.v. phenylephrine) were not altered by chronic lesions of NTS, indicating vascular reactivity to sympathetic stimulation is normal. Transection of the spinal cord at T1 profoundly decreased AP and was not further reduced by chlorisondamine in control or denervated rats. Inhibition of the rostral ventrolateral medulla (RVLM) by microinjections of muscimol (100 pmol/side) decreased AP to levels not further reduced by chlorisondamine in control rats, rats with SAD, and rats with NTS lesions. Blockade of GABA(A) receptors in the RVLM (50 pmol/side bicuculline) increased AP similarly in control rats and denervated rats. In agreement, inhibition of the caudal ventrolateral medulla (CVLM) by microinjections of muscimol or blockade of glutamatergic inputs (2.7 nmol/side kynurenate) produced comparable increases in AP in control and denervated rats. These data suggest the RVLM continues to drive the SNA that regulates AP in the chronic absence of baroreceptor inputs. In addition, despite the absence of a tonic excitatory input from NTS, in chronic baroreceptor-denervated rats glutamatergic inputs drive the CVLM to tonically inhibit the RVLM. Baroreceptor-independent regulation of the ventrolateral medulla may underlie central mechanisms contributing to the long-term control of AP.     

Aldosterone-induced brain MAPK signaling and sympathetic excitation are angiotensin II type-1 receptor dependent

Angiotensin II (ANG II)-induced mitogen-activated protein kinase (MAPK) signaling upregulates angiotensin II type-1 receptors (AT(1)R) in hypothalamic paraventricular nucleus (PVN) and contributes to AT(1)R-mediated sympathetic excitation in heart failure. Aldosterone has similar effects to increase AT(1)R expression in the PVN and sympathetic drive. The present study was undertaken to determine whether aldosterone also activates the sympathetic nervous system via MAPK signaling and, if so, whether its effect is independent of ANG II and AT(1)R. In anesthetized rats, a 4-h intravenous infusion of aldosterone induced increases (P < 0.05) in phosphorylated (p-) p44/42 MAPK in PVN, PVN neuronal excitation, renal sympathetic nerve activity (RSNA), mean blood pressure (MBP), and heart rate (HR). Intracerebroventricular or bilateral PVN microinjection of the p44/42 MAPK inhibitor PD-98059 reduced the aldosterone-induced RSNA, HR, and MBP responses. Intracerebroventricular pretreatment (5 days earlier) with pooled small interfering RNAs targeting p44/42 MAPK reduced total and p-p44/42 MAPK, aldosterone-induced c-Fos expression in the PVN, and the aldosterone-induced increases in RSNA, HR, and MBP. Intracerebroventricular infusion of either the mineralocorticoid receptor antagonist RU-28318 or the AT(1)R antagonist losartan blocked aldosterone-induced phosphorylation of p44/42 MAPK and prevented the increases in RSNA, HR, and MBP. These data suggest that aldosterone-induced sympathetic excitation depends upon that AT(1)R-induced MAPK signaling in the brain. The short time course of this interaction suggests a nongenomic mechanism, perhaps via an aldosterone-induced transactivation of the AT(1)R as described in peripheral tissues.     

Role of the area postrema in angiotensin II modulation of baroreflex control of heart rate in conscious mice

This study reports the effects of angiotensin II (ANG II), arginine vasopression (AVP), phenylephrine (PE), and sodium nitroprusside (SNP) on baroreflex control of heart rate in the presence and absence of the area postrema (AP) in conscious mice. In intact, sham-lesioned mice, baroreflex-induced decreases in heart rate due to increases in arterial pressure with intravenous infusions of ANG II were significantly less than those observed with similar increases in arterial pressure with PE (slope: -3.0 +/- 0.9 vs. -8.1 +/- 1.5 beats x min(-1) x mmHg(-1)). Baroreflex-induced decreases in heart rate due to increases in arterial pressure with intravenous infusions of AVP were the same as those observed with PE in sham animals (slope: -5.8 +/- 0.7 vs. -8.1 +/- 1.5 beats x min(-1) x mmHg(-1)). After the AP was lesioned, the slope of baroreflex inhibition of heart rate was the same whether pressure was increased with ANG II, AVP, or PE. The slope of the baroreflex-induced increases in heart rate due to decreases in arterial blood pressure with SNP were the same in sham- and AP-lesioned animals. These results indicate that, similar to other species, in mice the ability of ANG II to acutely reset baroreflex control of heart rate is dependent on an intact AP.     

Sympathetic nerve activity in the superior cervical ganglia increases in response to imposed increases in arterial pressure

Sympathetic vasoconstriction of cerebral vessels has been proposed to be a protective mechanism for the brain, limiting cerebral perfusion and microcirculatory pressure during transient increases in arterial pressure. To furnish direct neural evidence for this proposition, we aimed to develop a method for recording cerebral sympathetic nerve activity (SNA) from the superior cervical ganglion (SCG). We hypothesized that SNA recorded from the SCG increases during imposed hypertension, but not during hypotension. Lambs (n = 11) were anesthetized (alpha-chloralose, 20 mg.kg(-1).h(-1)) and ventilated. SNA was measured using 25-microm tungsten microelectrodes inserted into the SCG. Arterial blood pressure (AP) was pharmacologically raised (adrenaline, phenylephrine, or ANG II, 1-50 microg/kg iv), mechanically raised (intravascular balloon in the thoracic aorta), or lowered (sodium nitroprusside, 1-50 microg/kg iv). In response to adrenaline (n = 10), mean AP increased 135 +/- 10% from baseline (mean +/- SE), and the RMS value of SNA (Square Root of the Mean of the Squares, SNA(RMS)) increased 255 +/- 120%. In response to mechanically induced hypertension, mean AP increased 43 +/- 3%, and SNA(RMS) increased 53 +/- 13%. Generally, (9 of 10 animals), SNA(RMS) did not increase, as AP was lowered with sodium nitroprusside. Using a new model for direct recording of cerebral SNA from the SCG, we have demonstrated that SNA increases in response to large induced rises, but not falls, in AP. These findings furnish direct support for the proposed protective role for sympathetic nerves in the cerebral circulation.     

Baroreflex control of lumbar and renal sympathetic nerve activity in conscious rats

This study compared the baroreflex control of lumbar and renal sympathetic nerve activity (SNA) in conscious rats. Arterial pressure (AP) and lumbar and renal SNA were simultaneously recorded in six freely behaving rats. Pharmacological estimates of lumbar and renal sympathetic baroreflex sensitivity (BRS) were obtained by means of the sequential intravenous administration of sodium nitroprusside and phenylephrine. Sympathetic BRS was significantly (P < 0.05) lower for lumbar [3.0 +/- 0.4 normalized units (NU)/mmHg] than for renal (7.6 +/- 0.6 NU/mmHg) SNA. During a 219-min baseline period, spontaneous lumbar and renal BRS were continuously assessed by computing the gain of the transfer function relating AP and SNA at heart rate frequency over consecutive 61.4-s periods. The transfer gain was considered only when coherence between AP and SNA significantly differed from zero, which was verified in 99 +/- 1 and 96 +/- 3% of cases for lumbar and renal SNA, respectively. When averaged over the entire baseline period, spontaneous BRS was significantly (P < 0.05) lower for lumbar (1.3 +/- 0.2 NU/mmHg) than for renal (2.3 +/- 0.3 NU/mmHg) SNA. For both SNAs, spontaneous BRS showed marked fluctuations (variation coefficients were 26 +/- 2 and 28 +/- 2% for lumbar and renal SNA, respectively). These fluctuations were positively correlated in five of six rats (R = 0.44 +/- 0.06; n = 204 +/- 8; P < 0.0001). We conclude that in conscious rats, the baroreflex control of lumbar and renal SNA shows quantitative differences but is modulated in a mostly coordinated way.     

Time-dependent changes in autonomic control of splanchnic vascular resistance and heart rate in ANG II-salt hypertension

Previous studies suggest that ANG II-induced hypertension in rats fed a high-salt (HS) diet (ANG II-salt hypertension) has a neurogenic component dependent on an enhanced sympathetic tone to the splanchnic veins and independent from changes in sympathetic nerve activity to the kidney or hind limb. The purpose of this study was to extend these findings and test whether altered autonomic control of splanchnic resistance arteries and the heart also contributes to the neurogenic component. Mean arterial pressure (MAP), heart rate (HR), superior mesenteric artery blood flow, and mesenteric vascular resistance (MVR) were measured during 4 control days, 14 days of ANG II delivered subcutaneously (150 ng·kg(-1)·min(-1)), and 4 days of recovery in conscious rats fed a HS (2% NaCl) or low-salt (LS; 0.1% NaCl) diet. Autonomic effects on MAP, HR, and MVR were assessed by acute ganglionic blockade with hexamethonium (20 mg/kg iv) on day 3 of control, days 1, 3, 5, 7, 10, and 13 of ANG II, and day 4 of recovery. MVR increased during ANG II infusion in HS and LS rats but remained elevated only in HS rats. Additionally, the MVR response to hexamethonium was enhanced on days 10 and 13 of ANG II selectively in HS rats. Compared with LS rats, HR in HS rats was higher during the 2nd wk of ANG II, and its response to hexamethonium was greater on days 7, 10, and 13 of ANG II. These results suggest that ANG II-salt hypertension is associated with delayed changes in autonomic control of splanchnic resistance arteries and the heart.     

Differential sympathetic and angiotensinergic responses in rats submitted to low- or high-salt diet

The present study was designed to evaluate, in Wistar rats, the effect of high- or low-salt diet on the hemodynamic parameters and on the renal and lumbar sympathetic nerve activity. The renal gene expression of the renin angiotensin system components was also evaluated, aiming to find some correlation between salt intake, sodium homeostasis and blood pressure increase. Male Wistar rats received low (0.06% Na, TD 92141-Harlan Teklad), a normal (0.5% Na, TD 92140), or a high-salt diet (3.12% Na, TD 92142) from weaning to adulthood. Hemodynamic parameters such as cardiac output and total peripheral resistance, and the renal and lumbar sympathetic nerve activity were determined (n=45). Plasma renin activity, plasma and renal content of angiotensin (ANG) I and II, and the renal mRNA expression of angiotensinogen, renin, AT1 and AT2 receptors were also measured (n=24). Compared to normal- and low-salt diet-, high-salt-treated rats were hypertensive and developed an increase (P<0.05) in total peripheral resistance and lumbar sympathetic nerve activity. A decrease in renal renin and angiotensinogen-mRNAs and in plasma ANG II and plasma renin activity was also found in salt overloaded animals. The renal sympathetic nerve activity was higher (P<0.05) in low- compared to high-salt-treated rats, and was associated with an increase (P<0.05) in renal ANG I and II and with a decrease (P<0.05) in AT2 renal mRNA. Plasma ANG I and II and plasma renin activity were higher in low- than in normal-salt rats. Our results show that increased blood pressure is associated with increases in lumbar sympathetic nerve activity and total peripheral resistance in high-salt-treated rats. However, in low-salt-treated rats an increase in the renal sympathetic nerve was correlated with an increase in the renal content of ANG I and II and with a decrease in AT2 renal mRNA. These changes are probably in favor of the antinatriuretic response and the sodium homeostasis in the low-salt group.     

Baroreflex depression persists in the early phase after hypertension reversal

The baroreflex control of heart rate (HR) was evaluated in conscious chronic renal hypertensive rats (RHR; 1K-1C, 2 mo) under control conditions and after reversal of hypertension by unclipping the renal artery or sodium nitroprusside infusion. Unclipping and nitroprusside infusion were both followed by significant decreases in the mean arterial pressure (unclipping: from 199 +/- 4 to 153 +/- 8 mmHg; nitroprusside infusion: from 197 +/- 9 to 166 +/- 6 mmHg) as well as slight and significant increases, respectively, in the baroreflex bradycardic response index (unclipping: from 0.2 +/- 0.04 to 0.6 +/- 0.1 beats x min(-1) x mmHg(-1); nitroprusside infusion: from 0.1 +/- 0.04 to 0.5 +/- 0.1 beats x min(-1) x mmHg(-1)). However, this index was still depressed compared with that for normotensive control rats (2.1 +/- 0.2 beats x min(-1) x mmHg(-1)). The index for the baroreflex tachycardic response was also depressed under control conditions and remained unchanged after hypertension reversal. RHR possessed markedly attenuated vagal tone as demonstrated by pharmacological blockade of parasympathetic and sympathetic control of HR with methylatropine and propranolol, respectively. A reduced bradycardic response was also observed in anesthetized RHR during electrical stimulation of the vagus nerve or methacholine chloride injection, indicating impairment of efferent vagal influence over the HR. Together, these data indicate that 2 h after hypertension reversal in RHR, the previously described normalization of baroreceptor gain occurs independent of the minimal or lack of recovery of baroreflex control over HR.