侧脑室注射Orexin-1受体拮抗剂对大鼠心血管效应的影响

目的:用侧脑室微量注射和免疫组化方法研究食欲素-1受体(OX1R)拮抗剂SB408124对麻醉大鼠的心血管效应及其作用机制。方法:雄性SD大鼠,侧脑室微量注射SB408124,及甲硝阿托品、六甲溴铵静脉注射预处理后侧脑室注射SB408124,观测动脉血压(MAP)和心率(HR)的变化。然后,用免疫组化方法检测侧脑室注射SB408124对大鼠脑延髓头端腹外侧区(RVLM)内酪氨酸羟化酶(TH)阳性神经元的影响。结果:侧脑室注射SB408124可显著降低麻醉大鼠的MAP和HR,但是HR变化不如MAP变化明显。应用六甲溴铵可完全阻断SB408124的心血管效应,但甲硝阿托品不能阻断SB408124的心血管效应。侧脑室注射SB408124可使鼠脑延髓头端腹外侧区内酪氨酸羟化酶阳性神经元的数量显著降低。结论:侧脑室注射OX1R拮抗剂SB408124可显著降低麻醉大鼠的MAP和HR,其作用主要是通过抑制交感神经系统的活性而实现的。     

延髓腹外侧区微量注射L－NNA和SNP对大鼠血压、心率和肾交感神经活动的影响

在麻醉大鼠观察了向延髓腹外侧区微量注射ＮＯ合成酶抑制剂Ｎ－硝基左旋精氨酸（ＬＮＮＡ）和硝普钢（ＳＮＰ）对血压、心率和肾交感神经活动的影响,旨在探讨中枢左旋精氨酸－ＮＯ通路在动脉血压调节中的作用及其机制。实验结果如下：（１）向延髓腹外侧头端区（ＲＶＬＭ）注射Ｌ－ＮＮＡ后,平均动脉压（ＭＡＰ）升高,肾交感神经活动（ＲＳＮＡ）增强;心率（ＨＲ）减慢,但无统计学意义。ＭＡＰ和ＲＳＮＡ的变化持续３０ｍｉｎ以上;此效应可被预先静注左旋精氨酸所逆转。（２）向ＲＶＬＭ微量注射ＳＮＰ,ＭＡＰ降低,ＲＳＮＡ减弱;但ＨＲ的变化无统计学意义。（３）向延髓腹外侧尾端区（ＣＶＬＭ）注射Ｌ－ＮＮＡ,ＭＡＰ降低,ＨＲ减慢,ＲＳＮＡ减弱。（４）向ＣＶＬＭ微量注射ＳＮＰ,ＭＡＰ升高,ＲＳＮＡ增强,而心率无明显变化。以上结果表明,中枢左旋精氨酸－ＮＯ通路对延髓腹外侧部的神经元活动有调变作用。     

Effect of converting enzyme inhibition with captopril on baroreflex sensitivity

Clinical and experimental data suggest that both Captopril and angiotensin II (AII) reduce baroreflex responsiveness, and the main action of this converting enzyme inhibitor (CEI) seems clear to suppress AII synthesis. The aim of this work is to investigate this striking similarity of effects. We have verified that CEI (4 mg/kg) originates tachycardia significantly lower (P less than 0.001) than that produced in response to a similar hypotension elicited by an unspecific vasodilator: sodium nitroprusside (10-45 micrograms/kg min). CEI SQ 20881 has been reported to increase plasma vasopressin concentrations (AVP); this peptide is also known to modify baroreflex responses and has a small direct negative chronotropic effect. However, our determinations of AVP do not show any difference between the control group and the group treated with Captopril (4.78 +/- 0.87 and 5.26 +/- 0.19 pg/ml respectively). On the other hand, although CEI did not modify the rapid responses of heart rate (HR) to changes of mean arterial pressure (MAP), the decrease of MAP induced by nitroprusside was higher in the group treated with Captopril than in control group; it could mean a baroreflex ability decrease to buffer the hypotension. However, AII elicited a strong impairment of both rapid responses of HR and the buffering of hypotension produced by NP, these actions being suggested as centrally mediated. These results could indicate that the suppression of peripheral AII synthesis and therefore, the lack of pre- and postjunctional sympathetic potentiation owing to this hormone, is responsible for the absence of tachycardia under Captopril treatment.     

Nitric oxide at the CVLM is involved in the attenuation of the reflex bradycardia in renovascular hypertensive rats

Hypertension is associated to an increase in central oxidative stress and an attenuation of the baroreflex control of arterial pressure. The present study evaluated the effect of alterations in the levels of nitric oxide (NO) and superoxide anion in the caudal ventrolateral medulla (CVLM), a key area of the brainstem for the baroreflex control of arterial pressure, in renovascular hypertensive rats (2K1C). Baseline mean arterial pressure (MAP), heart rate (HR), and reflex bradycardia were evaluated 30 days after renal artery occlusion in anesthetized (urethane, 1.2 g/kg, i.p.) 2K1C or normotensive (SHAM) rats. The MAP, HR, and baroreflex control of HR were evaluated before and after CVLM microinjections of the non-selective NOS inhibitor L-NAME (10 nmol), the NO precursor L-ARG (50 nmol), or the antioxidant ascorbic acid, Vit C (10 nmol). In both 2K1C and SHAM animals, CVLM microinjection of L-NAME produced a decrease in MAP, whereas L-ARG induced a significant increase in MAP. However, microinjection of Vit C into the CVLM produced a decrease in MAP and HR only in 2K1C and not in SHAM rats. Cardiovascular effects produced by microinjection of l-ARG into the CVLM were abolished by prior microinjection of L-NAME in the CVLM of 2K1C and SHAM rats. Microinjection of L-NAME into the CVLM increased the sensitivity of reflex bradycardia in 2K1C animals. In contrast, the CVLM microinjection of L-ARG reduced reflex bradycardia only in SHAM rats. Vit C in the CVLM did not change reflex bradycardia in either 2K1C or in SHAM rats. These results suggest that increased oxidative stress in the CVLM during hypertension contributes to the reduced baroreflex sensitivity and to maintain hypertension in the 2K1C model.     

Cholecystokinin selectively affects presympathetic vasomotor neurons and sympathetic vasomotor outflow

Cholecystokinin (CCK) is a potential mediator of gastrointestinal vasodilatation during digestion. To determine whether CCK influences sympathetic vasomotor function, we examined the effect of systemic CCK administration on mean arterial blood pressure (MAP), heart rate (HR), lumbar sympathetic nerve discharge (LSND), splanchnic sympathetic nerve discharge (SSND), and the discharge of presympathetic neurons of the rostral ventrolateral medulla (RVLM) in alpha-chloralose-anesthetized rats. CCK (1-8 microg/kg iv) reduced MAP, HR, and SSND and transiently increased LSND. Vagotomy abolished the effects of CCK on MAP and SSND as did the CCK-A receptor antagonist devazepide (0.5 mg/kg iv). The bradycardic effect of CCK was unaltered by vagotomy but abolished by devazepide. CCK increased superior mesenteric arterial conductance but did not alter iliac conductance. CCK inhibited a subpopulation (approximately 49%) of RVLM presympathetic neurons whereas approximately 28% of neurons tested were activated by CCK. The effects of CCK on RVLM neuronal discharge were blocked by devazepide. RVLM neurons inhibited by exogenous CCK acting via CCK-A receptors on vagal afferents may control sympathetic vasomotor outflow to the gastrointestinal tract vasculature.     

Role of antidiuretic activity in the inhibition of renin secretion by vasopressin in anesthetized dogs

The nature of the activity of vasopressin which is responsible for the inhibition of renin secretion was studied by comparing the effects of vasopressin (AVP) and analogs of AVP in anesthetized water-loaded dogs. Infusion of AVP (1.0 ng/kg/min) increased mean arterial pressure (MAP) and decreased heart rate (HR) and free water clearance (CH2O). Plasma renin activity (PRA) decreased from 11.9 +/- 4.7 to 3.8 +/- 1.7 ng/ml/3 hr (p less than 0.05). A selective antidiuretic agonist, 1-deamino-8-D-arginine vasopressin (1.0 ng/kg/min), which had no effect on MAP or HR but was effective as AVP in decreasing CH2O, decreased PRA from 13.5 +/- 4.6 to 7.0 +/- 2.9 ng/ml/3 hr (p less than 0.05). Infusion of a selective vasoconstrictor agonist, 2-phenylalanine-8-ornithine oxytocin (1.0 ng/kg/min), increased MAP and decreased HR but did not decrease CH2O or PRA. A vasoconstrictor antagonist, d(CH2)5Tyr(Me)AVP (10 micrograms/kg), completely blocked the MAP and HR responses to AVP but did not block the decrease in CH2O or PRA (5.9 +/- 1.8 to 2.9 +/- 1.6 ng/ml/3 hr) (p less than 0.001). Infusion of the 0.45% saline vehicle had no significant effect on MAP, HR, CH2O or PRA. These results indicate that the inhibition of renin secretion by vasopressin in anesthetized water-loaded dogs is due to its antidiuretic activity.     

alpha(2)-Adrenergic receptors in NTS facilitate baroreflex function in adult spontaneously hypertensive rats

We examined the effect of alpha(2)-adrenoreceptor blockade in the nucleus of the solitary tract (NTS) on baroreflex responses elicited by electrical stimulation of the left aortic depressor nerve (ADN) in urethane-anesthetized spontaneously hypertensive rats (SHR, n = 11) and normotensive Wistar-Kyoto rats (WKY, n = 11). ADN stimulation produced a frequency-dependent decrease in mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and heart rate (HR). In SHR, unilateral microinjection of idazoxan into the NTS markedly reduced baroreflex control of MAP, RSNA, and HR and had a disproportionately greater influence on baroreflex control of MAP than of RSNA. In WKY, idazoxan microinjections did not significantly alter baroreflex function relative to control vehicle injections. These results suggest that baroreflex regulation of arterial pressure in SHR is highly dependent on NTS adrenergic mechanisms. The reflex regulation of sympathetic outflow to the kidney is less influenced by the altered alpha(2)-adrenoreceptor mechanisms in SHR.     

失血引起兔肾神经和肾上腺交感神经活动的变化

本文观察了急性失血引起的戊巴比妥钠麻醉兔的肾交感神经活动(RSNA)和肾上腺交感神经活动(AdSNA)的变化。股动脉放血,在10min内使平均动脉压(MAP)下降至5.3kPa。失血过程中RSNA先兴奋后抑制,AdSNA则一直呈兴奋反应,这反应可由动脉压力感受器去神经而消失。失血前和失血后切断迷走神经均可翻转失血引起的RSNA抑制,但不能阻断AdSNA的兴奋反应。静脉注射纳洛酮和延髓腹外侧头端(RVLM)微量注射纳洛酮可翻转失血引起的RSNA抑制,但对AdSNA兴奋反应无显著影响。失血引起心率(HR)和RSNA一样,但不能为纳洛酮所反转。上述结果表明:失血引起的RSNA抑制是由迷走神经传入纤维和阿片肽(尤其是RVLM中的阿片肽)参与所致,而AdSNA的兴奋则与动脉压力感受器传入纤维有关。     

Cardiac effects of hypocretin-1 in nucleus ambiguus

Although recent studies have reported hypocretin 1 (hcrt-1)-like-immunoreactivity (ir) within the region of the nucleus ambiguus (Amb) in the caudal brain stem, the function of hcrt-1 in the Amb on cardiovascular function is not known. Three series of experiments were done in male Wistar rats to investigate the effects of microinjections of hcrt-1 into Amb on heart rate (HR), mean arterial pressure (MAP), and the arterial baroreceptor reflex. In the first series, a detailed mapping of the distribution of hcrt-1- and hcrt-1 receptor (hcrtR-1)-like-ir was obtained of the Amb region. Although hcrt-1-like- and hcrtR-1-like-ir were found throughout the rostrocaudal extent of the Amb and adjacent ventrolateral medullary reticular formation, most of the hcrtR-1-like-ir was observed in the area just ventral to the compact formation of Amb, in the region of the external formation of the nucleus (Ambe). In the second series, the Amb region that contained hcrt-1 and hcrtR-1-ir was explored for sites that elicited changes in HR and MAP in urethane and alpha-chloralose-anesthetized rats. Microinjections of hcrt-1 (0.5-2.5 pmol) into the Ambe elicited a dose-related decrease in HR, with little or no direct change in MAP. The small decreases in MAP were found to be secondary to the HR changes. The largest bradycardia responses were elicited from sites in the Ambe. Administration (iv) of the muscarinic receptor antagonist atropine methyl bromide or ipsilateral vagotomy abolished the HR response, indicating that the HR response was due to activation of vagal cardiomotor neurons. In the final series, microinjections of hcrt-1 into the Ambe significantly potentiated the reflex bradycardia elicited by activation of the baroreflex as a result of the increased MAP after the intravenous injection of phenylephrine. These data suggest that hcrt-1 in the Ambe activates neuronal systems that alter the excitability of central circuits that reflexly control the circulation through the activation of vagal preganglionic cardioinhibitory neurons.     

Muscle metaboreflex control of coronary blood flow

We investigated the effect of muscle metaboreflex activation on left circumflex coronary blood flow (CBF) and vascular conductance (CVC) in conscious, chronically instrumented dogs during treadmill exercise ranging from mild to severe workloads. Metaboreflex responses were also observed during mild exercise with constant heart rate (HR) of 225 beats/min and beta(1)-adrenergic receptor blockade to attenuate the substantial reflex increases in cardiac work. The muscle metaboreflex was activated via graded partial occlusion of hindlimb blood flow. During mild exercise, with muscle metaboreflex activation, hindlimb ischemia elicited significant reflex increases in mean arterial pressure (MAP), HR, and cardiac output (CO) (+39.0 +/- 5.2 mmHg, +29.9 +/- 7.7 beats/min, and +2.0 +/- 0.4 l/min, respectively; all changes, P < 0.05). CBF increased from 51.9 +/- 4.3 to 88.5 +/- 6.6 ml/min, (P < 0.05), whereas no significant change in CVC occurred (0.56 +/- 0.06 vs. 0.59 +/- 0.05 ml. min(-1). mmHg(-1); P > 0.05). Similar responses were observed during moderate exercise. In contrast, with metaboreflex activation during severe exercise, no further increases in CO or HR occurred, the increases in MAP and CBF were attenuated, and a significant reduction in CVC was observed (1.00 +/- 0.12 vs. 0.90 +/- 0.13 ml. min(-1). mmHg(-1); P < 0.05). Similarly, when the metaboreflex was activated during mild exercise with the rise in cardiac work lessened (via constant HR and beta(1)-blockade), no increase in CO occurred, the MAP and CBF responses were attenuated (+15.6 +/- 4.5 mmHg, +8.3 +/- 2 ml/min), and CVC significantly decreased from 0.63 +/- 0.11 to 0.53 +/- 0.10 ml. min(-1). mmHg(-1). We conclude that the muscle metaboreflex induced increases in sympathetic nerve activity to the heart functionally vasoconstricts the coronary vasculature.     

The cardiovascular actions of centrally administered neuropeptide Y

The cardiovascular actions of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY) were examined in conscious, unrestrained rats. A prolonged decrease in heart rate (HR) and a fall in mean arterial pressure (MAP) were obtained following i.c.v. administration of NPY (1 and 10 micrograms). Passive immunization with an antiserum directed against NPY confirmed that the slowing of HR following i.c.v. administration of NPY was mediated via a central nervous mechanism and not from leakage of NPY out of the brain. Administration of NPY into different brain parenchymal regions identified a putative site of action in the rostral region of the solitary tract. The mechanism of the decrease in HR caused by centrally administered NPY was investigated by i.c.v. administration of NPY to animals that were pretreated with agents that altered autonomic tone. Administration of NPY to atropine-treated animals produced a reversal of the atropine-induced tachycardia, suggesting that the NPY-induced decrease in HR was not due to augmented vagal tone. However, administration of NPY to animals pretreated with propranolol did not significantly lower HR below that obtained with propranolol alone. These data suggest that i.c.v. administration of NPY may cause a decrease in cardiac sympathetic outflow. The effects of centrally administered NPY on baroreflex function were studied. The changes in HR caused by NPY did not significantly alter baroreflex set-point or gain. These studies provide evidence that NPY acted within a brainstem region to decrease sympathetic nervous outflow, resulting in a decrease in HR and MAP.     

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.     

延髓腹外侧头端区注射肾上腺髓质素对大鼠血压、心率和肾交感神经活动的影响

本研究在 3 4只麻醉Sprague Dawley大鼠观察了延髓腹外侧头端区内微量注射肾上腺髓质素 ( 10μmol/L ,2 0 0nl)对平均动脉压 (MAP)、心率 (HR)和肾交感神经放电 (RSNA)的影响。实验结果如下 :( 1)延髓腹外侧头端区内微量注射肾上腺髓质素可引起MAP、HR、和RSNA明显增加 ,分别由 99 0 9± 3 3 2mmHg ,3 70 78± 7 84bpm和 10 0± 0 %增至 113 5 7± 3 64mmHg (P <0 0 0 1) ,3 83 2 8± 7 3 8bpm (P <0 0 0 1)和 12 3 72±2 74% (P <0 0 0 1) ;( 2 )降钙素基因相关肽受体阻断剂CGRP8 3 7( 10 0 μmol/L ,2 0 0nl)不能阻断肾上腺髓质素的上述效应 ;( 3 )静脉注射NO前体L 精氨酸 ( 10 0mg/kg ,0 2ml)可消除肾上腺髓质素的上述效应。以上结果提示 ,肾上腺髓质素作用于延髓腹外侧头端区可产生显著的心血管作用 ,此作用不是由降钙素基因相关肽受体介导 ,但可被NO所阻断     

Cerebral circulation during mild +Gz hypergravity by short-arm human centrifuge

We examined changes in cerebral circulation in 15 healthy men during exposure to mild +Gz hypergravity (1.5 Gz, head-to-foot) using a short-arm centrifuge. Continuous arterial pressure waveform (tonometry), cerebral blood flow (CBF) velocity in the middle cerebral artery (transcranial Doppler ultrasonography), and partial pressure of end-tidal carbon dioxide (ETco(2)) were measured in the sitting position (1 Gz) and during 21 min of exposure to mild hypergravity (1.5 Gz). Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis between beat-to-beat mean arterial pressure (MAP) and mean CBF velocity (MCBFV). Steady-state MAP did not change, but MCBFV was significantly reduced with 1.5 Gz (-7%). ETco(2) was also reduced (-12%). Variability of MAP increased significantly with 1.5 Gz in low (53%)- and high-frequency ranges (88%), but variability of MCBFV did not change in these frequency ranges, resulting in significant decreases in transfer function gain between MAP and MCBFV (gain in low-frequency range, -17%; gain in high-frequency range, -13%). In contrast, all of these indexes in the very low-frequency range were unchanged. Transfer from arterial pressure oscillations to CBF fluctuations was thus suppressed in low- and high-frequency ranges. These results suggest that steady-state global CBF was reduced, but dynamic cerebral autoregulation in low- and high-frequency ranges was improved with stabilization of CBF fluctuations despite increases in arterial pressure oscillations during mild +Gz hypergravity. We speculate that this improvement in dynamic cerebral autoregulation within these frequency ranges may have been due to compensatory effects against the reduction in steady-state global CBF.     

Effects of angiotensins on day-night fluctuations and stress-induced changes in blood pressure

In this study we evaluated by telemetry the effects of ANG II and ANG-(1-7) infusion on the circadian rhythms of blood pressure (BP) and heart rate (HR) and on the cardiovascular adjustment resulting from restraint stress in rats. ANG II or ANG-(1-7) or vehicle were infused subcutaneously for 7 days. Restraint stress was carried out before, during, and after infusion at 7-day intervals. Parallel with an increase in MAP, ANG II infusion produced an inversion of MAP circadian rhythm with a significant MAP acrophase inversion. It also produced bradycardia during the first 3 days of infusion. Thereafter, HR progressively increased, reaching values similar to or above those of the control period at the end of the infusion period. HR circadian variation was not changed by ANG II infusion. Strikingly, ANG II significantly attenuated the increase in MAP induced by restraint stress without altering the HR response. ANG-(1-7) infusion produced a slight but significant decrease in MAP restricted to the daytime period. No significant changes in the MAP acrophase were observed. In addition, ANG-(1-7) infusion produced a small but significant sustained bradycardia. ANG-(1-7) did not change cardiovascular responses to restraint stress. These data indicate that ANG II can influence the activity of brain areas involved in the determination of stress-induced or circadian-dependent variations of blood pressure without changing HR fluctuations. A significant modulatory influence of ANG-(1-7) on basal MAP and HR is also suggested.     

Angiotensin II attenuates functional hyperemia in the mouse somatosensory cortex

We investigated whether angiotensin II (ANG II), a peptide that plays a central role in the genesis of hypertension, alters the coupling between synaptic activity and cerebral blood flow (CBF), a critical homeostatic mechanism that assures adequate cerebral perfusion to active brain regions. The somatosensory cortex was activated by stroking the facial whiskers in anesthetized C57BL/6J mice while local CBF was recorded by laser-Doppler flowmetry. Intravenous ANG II infusion (0.25 mug.kg-1.min-1) increased mean arterial pressure (MAP) from 82 +/- 2 to 102 +/- 3 mmHg (P < 0.05) without affecting resting CBF (P > 0.05). ANG II attenuated the CBF increase produced by whisker stimulation by 65% (P < 0.05) but did not affect the response to hypercapnia or to neocortical application of the nitric oxide donor S-nitroso-N-acetyl penicillamine (P > 0.05). The effect of ANG II on functional hyperemia persisted if the elevation in MAP was offset by controlled hemorrhage or prevented by topical application of the peptide to the activated cortex. ANG II did not reduce the amplitude of the P1 wave of the field potentials evoked by whisker stimulation (P > 0.05). Infusion of phenylephrine increased MAP (P > 0.05 from ANG II) but did not alter the functional hyperemic response (P > 0.05). The data suggest that ANG II alters the coupling between CBF and neural activity. The mechanisms of the effect are not related to the elevation in MAP and/or to inhibition of the synaptic activity evoked by whisker stimulation. The imbalance between CBF and neural activity induced by ANG II may alter the homeostasis of the neuronal microenvironment and contribute to brain dysfunction during ANG II-induced hypertension.     

Medullary pathways mediating the parasubthalamic nucleus depressor response

The parasubthalamic nucleus (PSTN) projects extensively to the nucleus of the solitary tract (NTS); however, the function of PSTN in cardiovascular regulation is unknown. Experiments were done in alpha-chloralose anesthetized, paralyzed, and artificially ventilated rats to investigate the effect of glutamate (10 nl, 0.25 M) activation of PSTN neurons on mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). Glutamate stimulation of PSTN elicited depressor (-20.4 +/- 0.7 mmHg) and bradycardia (-26.0 +/- 1.0 beats/min) responses and decreases in RSNA (67 +/- 17%). Administration (intravenous) of atropine methyl bromide attenuated the bradycardia response (46%), but had no effect on the MAP response. Subsequent intravenous administration of hexamethonium bromide blocked both the remaining bradycardia and depressor responses. Bilateral microinjection of the synaptic blocker CoCl(2) into the caudal NTS region attenuated the PSTN depressor and bradycardia responses by 92% and 94%, respectively. Additionally, prior glutamate activation of neurons in the ipsilateral NTS did not alter the magnitude of the MAP response to stimulation of PSTN, but potentiated HR response by 35%. Finally, PSTN stimulation increased the magnitude of the reflex bradycardia to activation of arterial baroreceptors. These data indicate that activation of neurons in the PSTN elicits a decrease in MAP due to sympathoinhibition and a cardiac slowing that involves both vagal excitation and sympathoinhibition. In addition, these data suggest that the PSTN depressor effects on circulation are mediated in part through activation of NTS neurons involved in baroreflex function.     

Pressor effects of orexins injected intracisternally and to rostral ventrolateral medulla of anesthetized rats

Orexin A and B, two recently isolated hypothalamic peptides, have been reported to increase food consumption upon intracerebroventricular injections in rats. In addition to the hypothalamus, orexin A-immunoreactive fibers have been observed in several areas of the medulla that are associated with cardiovascular functions. The present study was undertaken to evaluate the hypothesis that orexins may influence cardiovascular response by interacting with neurons in the medulla. Intracisternal injections of orexins A (0.0056-7.0 nmol) or B (0.028-0.28 nmol) dose dependently increased mean arterial pressure (MAP) by 4-27 mmHg and heart rate (HR) by 26-80 beats/min in urethan-anesthetized rats, with orexin A being more effective in this regard. MAP and HR were not changed by intravenous injection of orexins at higher concentrations. Microinjection of orexin A (14 pmol/50.6 nl) to the rostral ventrolateral medulla, which was confirmed by histological examination, increased MAP and HR. Our results indicate that, in addition to a role in positive feeding behavior, orexins may enhance cardiovascular response via an action on medullary neurons.     

Nitric oxide-independent effects of tempol on sympathetic nerve activity and blood pressure in DOCA-salt rats

The role of sympathetic nerves and nitric oxide (NO) in tempol-induced cardiovascular responses was evaluated in urethane-anesthetized sham and deoxycorticosterone acetate (DOCA)-salt-treated (DOCA-salt) rats. Tempol (30-300 micromol/kg iv), a superoxide (O) scavenger, decreased renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) in DOCA-salt and sham rats. The antioxidants tiron and ascorbate did not alter MAP, HR, or RSNA in any rat. Tempol responses were unaffected after sham rats were treated with N(G)-nitro-L-arginine (L-NNA, 13 mg/kg). In DOCA-salt rats, L-NNA reduced tempol-induced depressor responses but not the inhibition of HR or RSNA. Tempol did not significantly decrease MAP, HR, or RSNA after hexamethonium (30 mg/kg iv) treatment in any rat. Dihydroethidine histochemistry revealed increased O levels in arteries and veins from DOCA-salt rats. Tempol treatment in vitro reduced O levels in arteries and veins from DOCA-salt rats. In conclusion, tempol-induced depressor responses are mediated largely by NO-independent sympathoinhibition in sham and DOCA-salt rats. There is an additional interaction between NO and tempol that contributes to depressor responses in DOCA-salt rats.