Differential cardiovascular effects of central clonidine and B-HT 920 in conscious rats

The effect of intracerebroventricular (i.c.v.) injection of the alpha 2-adrenoceptor agonists clonidine and B-HT 920 on mean arterial pressure (MAP), heart rate (HR), and plasma concentrations of noradrenaline and adrenaline was examined in conscious unrestrained rats. The injection of 1.0 microgram clonidine significantly decreased MAP and slightly decreased HR. Plasma noradrenaline and adrenaline levels were slightly but not significantly decreased after the injection of 1 microgram clonidine. In contrast, the injection of 0.1-10.0 micrograms B-HT 920 increased MAP and decreased HR. Plasma noradrenaline and adrenaline levels were slightly increased after the injection of the 1- and 10-micrograms doses. The i.c.v. injection of the alpha 2-antagonist rauwolscine slightly but not significantly increased MAP and plasma noradrenaline and adrenaline levels. The responses to i.c.v. injection of clonidine and B-HT 920 were not changed by prior administration of rauwolscine. Neither the pressor response to B-HT 920 nor the depressor response to clonidine was abolished by rauwolscine, suggesting that neither response was mediated by alpha 2-adrenoceptors.     

FMRF-amide and L-Arg-L-Phe increase blood pressure and heart rate in the anaesthetised rat by central stimulation of the sympathetic nervous system

The neuropeptide FMRFamide (L-Phe-L-Met-L-Arg-L-Phe-NH2) increases mean arterial blood pressure (MABP) and heart rate (HR) in the anaesthetised rat at concentrations ranging from 10-1000 micrograms/kg. Here, we demonstrate that peptides containing L-arginyl-L-phenylalanine (L-Arg-L-Phe), the C-terminal sequence of FMRFamide, mimic its haemodynamic effects. L-Arg-L-Phe was approximately 4 fold more potent in increasing MABP and HR than FMRFamide. In 40 different peptides investigated, the following order of potency of the effective compounds was established: L-Arg-L-Phe-L-Ala = L-Arg-L-Phe greater than FMRFamide greater than L-Met-L-Arg-L-Phe = L-Arg-L-Trp greater than L-Arg-L-Tyr greater than D-Arg-L-Phe = L-Arg-L-Phe-OMe greater than L-Arg-L-Leu = L-Arg-L-Ile greater than L-Lys-L-Phe greater than L-Arg-L-Met. L-Arg-L-Phe or FMRFamide did not cause any pressor response in pithed rats, indicating a central mechanism of action. In anaesthetised rats, intravenous injections of FMRFamide or L-Arg-L-Phe (100 micrograms/kg) were associated with a 2-3 fold increase in plasma noradrenaline levels, whereas plasma adrenaline levels remained unchanged. Thus, L-Arg-L-Phe may represent the active principle of FMRFamide acting by a central mechanism involving the release of noradrenaline from sympathetic nerve terminals.     

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.     

Central cardiovascular effects of baclofen in spontaneously hypertensive rats

This study was conducted to investigate the effects of centrally administered baclofen on blood pressure and heart rate in conscious spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Administration of baclofen (1.0 microgram/kg) into the lateral cerebral ventricle (icv) produced an increase in mean arterial pressure (MAP) in both SHR and WKY rats. The increase in MAP was significantly lower in SHR (13 +/- 3 mmHg) when compared with WKY (27 +/- 5 mmHg). The changes in heart rate (HR) were variable, from no change to a very small increase and did not differ significantly between SHR and WKY rats. The ability of baclofen to interfere with baroreceptor reflexes was also tested in separate experiments. In SHR, icv injection of baclofen (1.0 microgram/kg) significantly suppressed the pressor response and bradycardia evoked by phenylephrine 3.0 micrograms/kg iv, whereas in WKY, the pressor and HR responses to similar injections of phenylephrine were not affected by icv baclofen. Similarly, baclofen treatment modified hypotensive response and reflex tachycardia induced by nitroprusside (10.0 micrograms/kg) iv in SHR but not in WKY rats. Administration of sympathetic ganglionic blocker hexamethonium (HEX; 25 mg/kg) iv produced an equivalent decrease in MAP between SHR and WKY following icv injection of baclofen (1.0 microgram/kg). These results suggest that the effects of baclofen on the baroreceptor reflexes in SHR may not be mediated by a change in peripheral sympathetic tone.     

Cardiovascular effects of histamine administered intracerebroventricularly in critical haemorrhagic hypotension in rats.

The study was designed to determine the cardiovascular effects of histamine administered intracerebroventricularly (icv) in a rat model of volume-controlled haemorrhagic shock. The withdrawal of approximately 50% of total blood volume resulted in the death of all control saline icv treated animals within 30 min. Icv injection of histamine produced a prompt dose-dependent (0.1-100 nmol) and long-lasting (10-100 nmol) increase in mean arterial pressure (MAP), pulse pressure (PP) and heart rate (HR), with a 100% survival of 2h after treatment (100 nmol). The increase in MAP and HR after histamine administration in bled rats in comparison to the normovolaemic animals was 2.7-3.3- and 1.3-3.6-fold higher, respectively. Pretreatment with chlorpheniramine (50 nmol icv), H1 receptor antagonist, inhibited the increase in MAP, PP, HR and survival rate produced by histamine, while chlorpheniramine given alone had no effect. Neither ranitidine (50 nmol icv), H2 histamine receptor antagonist, nor thioperamide (50 nmol icv), H3 receptor blocker, influenced the histamine action, however, when given alone, both evoked the pressor effect with elongation of survival time. It can be concluded that histamine administered icv reverses the haemorrhagic shock conditions, and histamine H1 receptors are involved.     

Sympathetic hyperreactivity to air-jet stress in the chromosome 1 blood pressure quantitative trait locus congenic rats

A chromosome 1 blood pressure quantitative trait locus (QTL) was introgressed from the stroke-prone spontaneously hypertensive rats (SHRSP) to Wistar-Kyoto (WKY) rats. This congenic strain (WKYpch1.0) showed an exaggerated pressor response to both restraint and cold stress. In this study, we evaluated cardiovascular and sympathetic response to an air-jet stress and also examined the role of the brain renin-angiotensin system (RAS) in the stress response of WKYpch1.0. We measured mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) responses to air-jet stress in WKYpch1.0, WKY, and SHRSP. We also examined effects of intracerebroventricular administration of candesartan, an ANG II type 1 receptor blocker, on MAP and HR responses to air-jet stress. Baseline MAP in the WKYpch1.0 and WKY rats were comparable, while it was lower than that in SHRSP rats. Baseline HR did not differ among the strains. In WKYpch1.0, air-jet stress caused greater increase in MAP and RSNA than in WKY. The increase in RSNA was as large as that in SHRSP, whereas the increase in MAP was smaller than in SHRSP. Intracerebroventricular injection of a nondepressor dose of candesartan inhibited the stress-induced pressor response to a greater extent in WKYpch1.0 than in WKY. Intravenous injection of phenylephrine caused a presser effect comparable between WKYpch1.0 and WKY. These results suggest that the chromosome 1 blood pressure QTL congenic rat has a sympathetic hyperreactivity to an air-jet stress, which causes exaggerated pressor responses. The exaggerated response is at least partly mediated by the brain RAS.     

Increased pressor responses to pressor agents in spontaneously hypertensive rats.

Pressor reactivity to a variety of pressor agents after partial ganglionic blockade induced with hexamethonium was investigated in intact, in spinalized, and in chemically sympathectomized, spontaneously hypertensive rats (SHR). Responses of unanaesthetized 6-month-old SHR to noradrenaline, phenylephrine, and angiotensin after hexamethonium administration (32 mg/kg) markedly exceeded those of unanaesthetized, age-matched normotensive Wistar-Kyoto rats (WKR). Responses of anaesthetized SHR to noradrenaline after hexamethonium administration (16 mg/kg) were also increased at the hypertensive stages but not at the prehypertensive stages, when compared with those of anaesthetized normotensive Wistar rats of respective ages. In spinalized and chemically sympathectomized preparations after hexamethonium administration (16 mg/kg), noradrenaline produced equal increases in blood pressure in 6-month-old SHR and WKR. It is suggested that the functional sympathetic nervous system is important for the hyperreactivity of intact SHR.     

Cardiac and regional haemodynamic effects of endothelin-1 in rats subjected to critical haemorrhagic hypotension.

In the present study, we examined cardiac and regional haemodynamic effects of endothelin-1 (ET-1), a potent vasoconstrictive factor, in a rat model of pressure-controlled irreversible haemorrhagic shock resulting in the death of all control animals within 30 min. Experiments were carried out in male ethylurethane-anaesthetised Wistar rats subjected to hypotension of 20-25 mmHg, which resulted in bradycardia, an extreme decrease in cardiac index (CI) and an increase in total peripheral resistance index (TPRI), with reductions in renal (RBF), hindquarters (HBF) and mesenteric blood flow (MBF). ET-1 (50, 200 pmol/kg) administered intravenously at 5 min of critical hypotension produced increases in mean arterial pressure (MAP) and heart rate (HR), which were significantly higher than those in normotensive animals, and a 100% survival at 2 h after treatment. The effects were accompanied by a rise in CI, a decrease in TPRI, with increases in RBF and HBF and persistently lowered MBF, and an increase in circulating blood volume 20 min after treatment. The cardiovascular effects of ET-1 were inhibited by the ETA receptor antagonist BQ-123 (1 mg/kg), while the ETB receptor antagonist BQ-788 (3 mg/kg) had no effect. In conclusion, ET-1 acting via ETA receptors produces reversal of haemorrhagic hypotension in rats due to the mobilisation of blood from venous reservoirs, with the improvements in cardiac function and the perfusion of peripheral tissues.     

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.     

Hindlimb unloading alters nitric oxide and autonomic control of resting arterial pressure in conscious rats

After periods of microgravity or bed rest, individuals often exhibit reduced Vo(2 max), hypovolemia, cardiac and vascular effects, and autonomic dysfunction. Recently, alterations in expression of vascular and central nervous system NO synthase (NOS) have been observed in hindlimb-unloaded (HU) rats, a model used to simulate physiological effects of microgravity or bed rest. We examined the effects of 14 days of hindlimb unloading on hemodynamic responses to systemic NOS inhibition in conscious control and HU rats. Because differences in NO and autonomic regulation might occur after hindlimb unloading, we also evaluated potential differences in resting autonomic tone and effects of NOS inhibition after autonomic blockade. Administration of nitro-L-arginine methyl ester (L-NAME; 20 mg/kg iv) increased mean arterial pressure (MAP) to similar levels in control and HU rats. However, the change in MAP in response to L-NAME was less in HU rats, that had an elevated baseline MAP. In separate experiments, atropine (1 mg/kg iv) increased heart rate (HR) in control but not HU rats. Subsequent administration of the ganglionic blocker hexamethonium (30 mg/kg iv) decreased MAP and HR to a greater extent in HU rats. Administration of L-NAME after autonomic blockade increased MAP in both groups to a greater extent compared with intact conditions. However, the pressor response to L-NAME was still reduced in HU rats. These data suggest that hindlimb unloading in rats reduces peripheral NO as well as cardiac parasympathetic tone. Along with elevations in sympathetic tone, these effects likely contribute to alterations in vascular control and changes in autonomic reflex function following spaceflight or bed rest.     

Bacillus anthracis lethal toxin alters regulation of visceral sympathetic nerve discharge

Bacillus anthracis infection is a pathophysiological condition that is complicated by progressive decreases in mean arterial pressure (MAP). Lethal toxin (LeTx) is central to the pathogenesis of B. anthracis infection, and the sympathetic nervous system plays a critical role in physiological regulation of acute stressors. However, the effect of LeTx on sympathetic nerve discharge (SND), a critical link between central sympathetic neural circuits and MAP regulation, remains unknown. We determined visceral (renal, splenic, and adrenal) SND responses to continuous infusion of LeTx [lethal factor (100 μg/kg) + protective antigen (200 μg/kg) infused at 0.5 ml/h for ≤6 h] and vehicle (infused at 0.5 ml/h) in anesthetized, baroreceptor-intact and baroreceptor (sinoaortic)-denervated (SAD) Sprague-Dawley rats. LeTx infusions produced an initial state of cardiovascular and sympathetic nervous system activation in intact and SAD rats. Subsequent to peak LeTx-induced increases in arterial blood pressure, intact rats demonstrated a marked hypotension that was accompanied by significant reductions in SND (renal and splenic) and heart rate (HR) from peak levels. After peak LeTx-induced pressor and sympathoexcitatory responses in SAD rats, MAP, SND (renal, splenic, and adrenal), and HR were progressively and significantly reduced, supporting the hypothesis that LeTx alters the central regulation of sympathetic nerve outflow. These findings demonstrate that the regulation of visceral SND is altered in a complex manner during continuous anthrax LeTx infusions and suggest that sympathetic nervous system dysregulation may contribute to the marked hypotension accompanying B. anthracis infection.     

Adrenomedullary pressor responses to stimulation of the rostral hypothalamus in the rat: influence of adrenaline-induced vasodilation and reflex cardioinhibition

Electrical stimulation (100 Hz, 1 ms, 150 microA, 10 s) of the anterior hypothalamus in chloralose-anesthetized rats evoked a biphasic pressor response consisting of an initial sharp rise in arterial pressure at the onset of stimulation, followed by a second elevation after cessation of the stimulus. This response was accompanied by an increase in plasma noradrenaline and adrenaline levels. Peripheral sympathectomy with guanethidine selectively abolished the primary phase of the biphasic pressor response, while bilateral removal of the adrenal medulla eliminated only the secondary component. After alpha-adrenergic blockade with phentolamine, the primary phase of the stimulation-induced response was reduced while the secondary pressor component was blocked and replaced by a significant hypotension. The intravenous administration of sotalol enhanced the secondary pressor component without affecting the stimulation-induced plasma noradrenaline and adrenaline responses. After treatment with atropine, the secondary pressor effect was also potentiated, as the reflex bradycardia normally associated with the response was eliminated. A subsequent administration of sotalol in these rats further potentiated the secondary pressor component to stimulation. In rats treated with atropine and sotalol, the sympathetic vasomotor and the adrenomedullary pressor responses could be dissociated according to thresholds and stimulus frequency or current-response characteristics. The results suggest that in intact rats, adrenaline-induced vasodilation and reflex cardiac inhibition contribute to either reduce or mask the adrenomedullary component of the biphasic pressor response evoked by stimulation of the anterior hypothalamus. The study also raises the hypothesis of a dual regulation of both components of the sympathetic system in the anterior hypothalamic region.     

Bimodal effects of chronically administered neurokinin B (NKB) on in vivo and in vitro cardiovascular responses in female rats

The in vivo cardiovascular effects of acutely administered neurokinin B (NKB) have been attributed both to direct effects on vascular tone and to indirect effects on central neuroendocrine control of the circulation. We proposed: 1) that a modest long-term increase in plasma NKB levels would decrease mean arterial pressure (MAP) due to attenuated peripheral vascular tone, and 2) that chronic high-dose NKB would increase MAP, due to increased sympathetic outflow which would override the peripheral vasodilation. We examined the in vivo and in vitro cardiovascular effects of chronic peripheral NKB. Low- (1.8 nmol/h) or high- (20 nmol/h) dose NKB was infused into conscious female rats bearing telemetric pressure transducers. MAP, heart rate (HR) and the pressor responses to I.V. phenylephrine (PE, 8 microg) and angiotensin II (Ang II, 150 ng) were measured. Concentration-response curves of small mesenteric arteries were constructed to PE using wire myography. Low-dose NKB reduced basal MAP (88+/-2 mm Hg to 83+/-2 mm Hg), did not affect resting HR, reduced the pressor responses to PE, and attenuated the maximal constriction of mesenteric arteries to PE and KCl. By contrast, high-dose NKB increased basal MAP (86+/-1 mm Hg to 89+/-1 mm Hg), increased HR (350+/-3 beats/min to 371+/-3 beats/min), increased the pressor responses to Ang II and, contrary to our hypothesis, increased the maximum contractile responses of mesenteric arteries to PE and KCl. The cardiovascular effects of NKB are thus dose-dependent: whereas chronic low-dose NKB directly modulates vascular tone to reduce blood pressure, chronic high-dose NKB induces an increase in blood pressure through both central (indirect) and peripheral (direct) pathways.     

Systemic responses to carotid occlusion in the anesthetized rat.

We evaluated the effects of four standard anesthetization regimens on the systemic cardiovascular responses to bilateral common carotid artery occlusion in 28 adult male rats. Rats were randomly assigned to anesthesia groups: thiopental sodium (PT; 100 mg/kg ip), alpha-chloralose (CH; 100 mg/kg iv), ketamine hydrochloride plus acepromazine (KA; 135 mg/kg and 1.5 mg/kg sc), and pentobarbital sodium (PB; 50 mg/kg ip). PT and PB animals had similar baseline heart rates (HR; 333 and 345 beats/min, respectively) and arterial pressures (MAP; 126 and 118 mmHg, respectively), whereas both were lower in CH and KA (314 and 288 beats/min, 92 and 85 mmHg). During bilateral carotid occlusion, PT demonstrated the largest change in MAP (dMAP; +27 mmHg) but the smallest change in HR (dHR; +8 beats/min). CH and PB demonstrated similar dHR (+24 and +16 beats/min) and dMAP (+20 and +19 mmHg). KA demonstrated a significant dHR (+14 beats/min), but the average dMAP was not statistically significant (+3 mmHg). Therefore, carotid occlusion in rats anesthetized with PT, PB, or CH consistently elicits a systemic arterial pressor response comparable with that reported for conscious animals. When the magnitude and stability of baseline HR and MAP are also considered, PT and PB anesthetization seem to be the most reliable for evaluation of the carotid occlusion pressor response in rats.     

Hypothalamic angiotensinergic-noradrenergic systems interaction in fructose induced hypertension

OBJECTIVE: Several studies suggest the importance of the interaction between the renin angiotensin and sympathetic nervous systems in blood pressure control, especially in clinical situations such as the metabolic syndrome. Previously, we have demonstrated changes in noradrenergic hypothalamic control of blood pressure in an animal model of insulin resistance and hypertension. The aim of the present study was to evaluate the effects of the interaction between the noradrenergic and angiotensinergic systems on hypothalamic blood pressure regulation in fructose hypertensive rats. METHODS: In control (C) and fructose-fed hypertensive (F) rats, we studied: 1) the effects of hypothalamic perfusion of irbesartan (AT(1) angiotensin receptor antagonist, 50 and 500 microg ml(-1)) and metoprolol (beta(1) adrenergic receptor antagonist, 10 and 100 microg ml(-1)) on blood pressure, heart rate and noradrenaline intrahypothalamic levels, by means of the microdialysis technique; and 2) the effects of intrahypothalamic microinjection of angiotensin II alone or after metoprolol pre-administration, on blood pressure and heart rate. RESULTS: Meanwhile irbesartan perfusion did not modify neither mean arterial pressure (MAP) nor heart rate or noradrenaline hypothalamic levels in the C group, its highest dose diminished MAP (DeltaMAP: F: - 16.3+/-1 mm Hg, p<0.05) and noradrenaline levels (% of basal levels: 58+/-7%, p<0.05) in the F group, without affecting heart rate. Intrahypothalamic perfusion of metoprolol diminished MAP only in the F group (DeltaMAP: F: -12.1+/-1.1 mm Hg, p<0.05), but did not modify heart rate in both groups. On the other hand, it diminished noradrenaline hypothalamic levels in C (% of basal levels: 53+/-6%, p<0.05) but not in the F group. The pressor response to angiotensin II microinjection was increased in F rats (DeltaMAP: F: 13.3+/-1.5 mm Hg vs. C: 6.9+/-1.8 mm Hg; p<0.05). Previous administration of metoprolol markedly abolished this increment. CONCLUSIONS: Our results suggest the existence of an increase in AT(1) and beta(1) adrenergic receptors tone in the hypothalamus of F rats, which could be related to the increase in blood pressure present in this experimental model. On the other hand, considering that the enhanced pressor response to angiotensin II intrahypothalamic injection in F rats was abolished by previous administration of a beta(1) adrenergic receptor antagonist, these results would indicate that beta(1) adrenergic receptors activation participates in the pressor response to angiotensin II in this experimental model of insulin resistance and hypertension.     

Hemodynamic actions of endothelin in conscious and anesthetized dogs

The newly described endogenous peptide, endothelin, was administered to five chronically instrumented conditioned dogs. Endothelin produced significant and simultaneous increases in both heart rate (HR) and mean arterial pressure (MAP) in conscious dogs. Endothelin also produced significant increases in MAP in anesthetized animals. Ganglionic suppression induced by hexamethonium (10 mg/kg) and atropine (0.1 mg/kg) blocked HR responses and markedly inhibited the pressor responses to endothelin in conscious animals. These results suggest that endothelin in part acts to elevate blood pressure and heart rate through modification of autonomic nervous system tone. When endothelin and angiotensin II were administered in mole equivalent doses, angiotensin II produced a pressor response of greater magnitude than did endothelin in conscious animals.     

胍丁胺对Dahl盐敏感型高血压大鼠和Dahl盐抵抗型大鼠血流动力学的影响

在麻醉Dahl盐敏感型(DS)高血压大鼠和Dahl盐抵抗型(DR)正常血压大鼠,研究了静注胍丁胺(agmatine,AGM)对血流动力学的影响.结果显示(1)静注AGM(1,10,20mg/kg)可剂量依赖性地降低DS和DR大鼠的HR,MAP,LVP,±LVdp/dtmax,CI和TPRI.在DS高血压大鼠,MAP,LVP,±LVdp/dtmax和TPRI较DR正常血压大鼠下降幅度要大;而HR和CI在两种大鼠下降幅度无差异.需特别提出的是,DS高血压大鼠在静注高剂量AGM(20mg/kg)后,各项血流动力学指标出现先降低而后升高的现象,这一结果在DR正常血压大鼠并未出现.(2)预先静注咪唑啉受体(IR)和α2-肾上腺素能受体阻断剂(α2-AR)idazoxan(2.5mg/kg)可部分阻抑AGM的血流动力学效应.(3)预先静注α2-肾上腺素能受体阻断剂yohimbine(4mg/kg)同样可部分阻抑AGM的效应.(4)预先静注咪唑啉受体(I1)和α2-肾上腺素能受体阻断剂efaroxan(2.5mg/kg)则完全阻断AGM的血流动力学效应.以上结果表明,AGM可显著降低麻醉DR和DS大鼠的HR,MAP,LVP,±LVdp/dtmax,CI和TPRI;此效应似主要由I1-IR所介导,并有I2-IR和α2-AR参与.     

Pressor and tachycardic responses to intravenous substance P in anesthetized rats

Intravenous injection of 3–33 nmol/kg of substance P (SP) caused pressor and tachycardic responses in anesthetized rats. The responses were not blocked by a ganglion nicotinic receptor antagonist or by pithing. Pretreatment with reserpine blocked both responses. β-Adrenoceptor blockade attenuated only the tachycardic response, and -adrenoceptor blockade attenuated only the pressor response. These findings indicated that the effects of SP to increase blood pressure and heart rate are due to sympathetic ganglion stimulation. Studies with adrenalectomized rats showed that stimulation of the adrenals by SP contributes to both responses but makes a greater contribution to the tachycardic response. These observations raise the possibility that the tachykinin innervation of sympathetic ganglia and the adrenal medulla may be involved in the local regulation of blood pressure and heart rate.     

Chronic central infusion of aldosterone leads to sympathetic hyperreactivity and hypertension in Dahl S but not Dahl R rats

Six-week-old Dahl salt-sensitive (S) and -resistant (R) rats received for 2 wk an intracerebroventricular infusion of aldosterone (Aldo) (22.5 ng/h) or vehicle containing artificial cerebrospinal fluid (aCSF) with 0.15 M Na+. At 8 wk, mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were recorded in conscious rats at rest, in response to air stress, and to an intracerebroventricular injection of the alpha2-adrenoceptor agonists guanabenz or ouabain. Baroreflex control of RSNA and HR was estimated by using intravenous phenylephrine and nitroprusside. In Dahl S but not Dahl R rats, Aldo raised resting MAP by 20-25 mmHg, doubled sympathoexcitatory and pressor responses to air stress and sympathoinhibitory and depressor responses to guanabenz, and impaired baroreflex function. In Dahl S but not Dahl R rats, Aldo significantly increased content of ouabain-like compounds (OLC) in the hypothalamus and attenuated excitatory responses to ouabain. Aldo did not affect water intake, plasma electrolytes, or OLC in plasma and adrenal glands. In another set of three groups of Dahl S rats, Aldo dissolved in aCSF containing 0.16, 0.15, or 0.14 M Na+ was infused intracerebroventricularly for 2 wk. CSF Na+ concentration ([Na+]) showed only a nonsignificant increase, but resting MAP increased from 111 +/- 3 mmHg in rats with Aldo in 0.14 M Na+ to 131 +/- 3 and 147 +/- 3 mmHg with Aldo in 0.15 and 0.16 M Na+, respectively (P < 0.05 for both). These findings indicate that in Dahl S rats, intracerebroventricular infusion of Aldo causes similar central responses as high salt intake, i.e., increases in brain OLC content, sympathetic hyperreactivity, and hypertension. The extent of the increase in blood pressure (BP) by intracerebroventricular Aldo depends on the [Na+] in the vehicle. In Dahl R rats, intracerebroventricular Aldo did not increase brain OLC, sympathetic reactivity, and BP, suggesting that in this rat strain, a decrease in central responsiveness to mineralocorticoids may contribute to its salt-resistant nature.     

Effect of stellate ganglionectomy on basal cardiovascular function and responses to beta1-adrenoceptor blockade in the rat

Cardiac sympathetic nerve activity is an important short-term controller of cardiac function and arterial pressure. Studies also suggest that long-term increases in cardiac sympathetic nerve activity may contribute to hypertension, coronary artery disease, and cardiac remodeling in heart failure. However, our understanding of the role of cardiac sympathetic nerves in chronic models of cardiovascular disease has been limited by inadequate experimental approaches. The present study was conducted to develop a surgical method to surgically denervate the sympathetic nerves of the rat heart for long-term cardiovascular studies. We characterized the effect of cardiac sympathetic denervation on basal levels of mean arterial pressure (MAP) and heart rate (HR) and the responses to a chronic administration of atenolol, a beta1-adrenoceptor antagonist. Rats were instrumented with telemetry transmitters for continuous recording of MAP and HR. After a 4-day baseline period, the rats were subjected to bilateral stellate ganglionectomy (SGX; n=9) or sham surgery (Sham; n=8). Seven days following SGX or Sham, the rats were administered atenolol for 5 days, followed by a 7-day recovery period. Following a transient decrease, SGX had no effect on basal MAP but decreased HR compared with baseline and Sham rats. Five days of atenolol treatment decreased MAP similarly in SGX and Sham rats. Atenolol resulted in a marked bradycardia in Sham rats but had a neglible effects on HR in SGX rats. The measurement of the content of cardiac catecholamines in all cardiac chambers at the end of the study verified a successful sympathetic denervation. This study confirms that bilateral SGX is a useful method to study the contribution of cardiac sympathetic nerves on the regulation of cardiac function. Moreover, these results suggest that cardiac sympathetic nerves are relatively unimportant in maintaining the basal level of MAP or the depressor response to atenolol in conscious, unrestrained rats.