Rostral ventral medulla 5-HT1A receptors selectively inhibit the somatosympathetic reflex

The role of the 5-hydroxytryptamine (5-HT1A) receptors in the rostral ventrolateral medulla (RVLM) on somatosympathetic, baroreceptor, and chemoreceptor reflexes was examined in anesthetized rats. Microinjection of the selective 5-HT1A agonist 8-hydroxy-di-n-propylamino tetralin (8-OH-DPAT) decreased arterial blood pressure and splanchnic sympathetic nerve activity (SNA). Electrical stimulation of the hindlimb evoked early and late excitatory sympathetic responses. Bilateral microinjection in the RVLM of 8-OH-DPAT markedly attenuated both the early and late responses. This potent inhibition of the somatosympathetic reflex persisted even after SNA and arterial blood pressure returned to preinjection levels. Preinjection of the selective 5-HT1A antagonist NAN-190 in the RVLM blocked the sympathoinhibitory effect of 8-OH-DPAT and attenuated the inhibitory effect on the somatosympathetic reflex. 8-OH-DPAT injected in the RVLM did not affect baroreceptor or chemoreceptor reflexes. Our findings suggest that activation of 5-HT1A receptors in the RVLM exerts a potent, selective inhibition on the somatosympathetic reflex.     

Comparison of somatosympathetic reflex in normotensive and spontaneously hypertensive rats

In chloralose anaesthetized and paralyzed normotensive (Wistar, Wistar--Kyoto) and spontaneously hypertensive rats (SHR), a somatosympathetic reflex in the cervical sympathetic trunk elicited by a single electrical shock to forelimb afferent fibres in the median nerve was recorded. It has been shown that the elicited response of SHR is similar to the response of normotensive rats. Amplitude of somatosympathetic reflex in SHR is larger than that of somatosympathetic reflex in normotensive animals. It is supposed that somatosympathetic reflex in hypertensive and normotensive rats is formed in the same way. However, reflex excitability of sympathetic nervous system in SHR is greater.     

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.     

Clonidine fails to reduce pressor responsiveness of conscious spontaneously hypertensive rats to vasopressin

Pressor responses and heart rate responses to intravenous injections (3.5-50.0 pmol/kg) of arginine vasopressin (AVP) were recorded in saline- and clonidine-treated spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Clonidine (20 micrograms/kg, i.v.) caused a marked fall of arterial pressure in SHR but not in WKY rats so that, 20 min after the injection of the alpha 2-adrenoceptor agonist, arterial pressure was similar in the two strains of rats. The curve expressing the relationship between the dose of AVP and the increase of arterial pressure for saline-treated SHR was positioned to the left of that for saline-treated WKY rats. This enhanced pressor responsiveness of SHR to AVP may have been related to impaired reflex activity since heart rate fell much less in SHR than in WKY rats for a given elevation in pressure. Pressure responses to AVP were augmented by clonidine in both SHR and WKY rats so that, similar to saline-treated rats, pressor responsiveness to the peptide was still greater in SHR. Heart rate responses to AVP were not altered significantly by clonidine. The results indicate that clonidine fails to enhance reflex activity and reduce pressor responsiveness of SHR to AVP. The increased pressor responsiveness of both SHR and WKY rats to AVP following clonidine was an unexpected finding and may be related to a peripheral interaction between alpha-adrenergic agonists and AVP.     

Somatosympathetic reflex in rats with various models of arterial hypertension

Spontaneous and reflex activities of sympathetic nerve were compared in animals with arterial hypertension of different aetiology. Reflex discharges elicited by single-shock stimulation of afferent fibres were recorded. In acute experiences on anaesthetized rats with renovascular and spontaneous (SHR) model of arterial hypertension, electric basal and evoked activity (somatosympathetic reflex) in cervical sympathetic trunk were recorded. It is shown, that the spontaneous electric activity in sympathetic nerve of hypertensive rats is larger than spontaneous activity of normotensive control animals. The somatosympathetic reflex in hypertensive rats differs from that of control animals. In rats with renovascular model of hypertension, the reflex magnitude is reduced, and in the SHR the reflex is increased. Time characteristics of the reflex in hypertensive rats differed among them. It is suggested that functional activities of the brain stem in rats with different arterial hypertension model are unequal.     

Evidence for functional alterations in the skeletal muscle mechanoreflex and metaboreflex in hypertensive rats

Exercise in hypertensive individuals elicits exaggerated increases in mean arterial pressure (MAP) and heart rate (HR) that potentially enhance the risk for adverse cardiac events or stroke. Evidence suggests that exercise pressor reflex function (EPR; a reflex originating in skeletal muscle) is exaggerated in this disease and contributes significantly to the potentiated cardiovascular responsiveness. However, the mechanism of EPR overactivity in hypertension remains unclear. EPR function is mediated by the muscle mechanoreflex (activated by stimulation of mechanically sensitive afferent fibers) and metaboreflex (activated by stimulation of chemically sensitive afferent fibers). Therefore, we hypothesized the enhanced cardiovascular response mediated by the EPR in hypertension is due to functional alterations in the muscle mechanoreflex and metaboreflex. To test this hypothesis, mechanically and chemically sensitive afferent fibers were selectively activated in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) decerebrate rats. Activation of mechanically sensitive fibers by passively stretching hindlimb muscle induced significantly greater increases in MAP and HR in SHR than WKY over a wide range of stimulus intensities. Activation of chemically sensitive fibers by administering capsaicin (0.01-1.00 microg/100 microl) into the hindlimb arterial supply induced increases in MAP that were significantly greater in SHR compared with WKY. However, HR responses to capsaicin were not different between the two groups at any dose. This data is consistent with the concept that the abnormal EPR control of MAP described previously in hypertension is mediated by both mechanoreflex and metaboreflex overactivity. In contrast, the previously reported alterations in the EPR control of HR in hypertension may be principally due to overactivity of the mechanically sensitive component of the reflex.     

Potentiation of pressor response to angiotensin II at the preoptic area in spontaneously hypertensive rat

Cardiovascular responses to angiotensin II(AII) at the preoptic area (POA) were compared between normotensive Wistar Kyoto rat (WKY) and spontaneously hypertensive rat(SHR) by measuring blood pressure and heart rate under unrestrained, conscious state via a catheter implanted chronically into the abdominal aorta and by injection of drugs into POA through a chronic guide cannula. AII injected into POA at doses of 0.3 ng and 1 ng produced a dose-dependent pressor response, accompanied with a slight decrease of heart rate, in both WKY and SHR. However, in SHR, the pressor response to AII was more than 2 times greater than that in WKY and was quick in onset and lasted about 30 min. When AII in combination with [Sar1, Ile8]-angiotensin II (0.5 microgram), an AII receptor antagonist, were simultaneously administered to POA, the pressor response to AII was strongly inhibited in both WKY and SHR. The results suggest that the pressor response to AII due to its receptor stimulation at POA is markedly potentiated in SHR.     

Increased superoxide anion in rostral ventrolateral medulla contributes to hypertension in spontaneously hypertensive rats via interactions with nitric oxide

Oxidative stress because of an excessive production of superoxide anion (O2*-) is associated with hypertension. The present study evaluated the hypothesis that in the rostral ventrolateral medulla (RVLM), where the premotor neurons for the maintenance of vascular vasomotor activity are located, increased O2*- contributes to hypertension in spontaneously hypertensive rats (SHR) by modulating the cardiovascular depressive actions of nitric oxide (NO). Compared with normotensive Wistar-Kyoto (WKY) rats, SHR manifested significantly increased basal O2*- production, along with reduced manganese superoxide dismutase (MnSOD) expression and activity, in the RVLM. The magnitude of hypotension, bradycardia, or suppression of sympathetic neurogenic vasomotor tone elicited by microinjection bilaterally into the RVLM of a membrane-permeable SOD mimetic, Mn(III)-tetrakis-(4-benzoic acid) porphyrin (MnTBAP), was also significantly larger in SHR. Transfection bilaterally into the RVLM of adenoviral vectors encoding endothelial nitric oxide synthase resulted in suppression of arterial pressure, heart rate, and sympathetic neurogenic vasomotor tone in both WKY rats and SHR. Microinjection of MnTBAP into the RVLM of SHR further normalized those cardiovascular parameters to the levels of WKY rats. We conclude that an elevated level of O2*- in the RVLM is associated with hypertension in SHR. More importantly, this elevated O2*- may contribute to hypertension by reducing the NO-promoted cardiovascular depression.     

Pressor responsiveness to vasopressin in spontaneously hypertensive rats

The present study was designed to find out whether pressor responsiveness to vasopressin (AVP) is altered in spontaneously hypertensive rats (SHR) in comparison with their normotensive controls (WKY). Blood pressure and heart rate changes after injection of graded doses of 2.5, 5.0 and 10.0 ng of AVP (Calbiochem) i.v. were compared in 9 conscious, unrestrained spontaneously hypertensive (SHR) and 11 normotensive Wistar Kyoto (WKY) rats, chronically instrumented with venous and arterial catheters. The threshold dose necessary to elicit a significant increase in blood pressure and reduction of heart rate was lower in WKY than in SHR. At each dose level the blood pressure elevation persisted for a longer period in WKY than in SHR. Bradycardia was greater in WKY than in SHR both in absolute terms and in relation to the blood pressure increase. Thus, the results reveal diminished pressor responsiveness to moderate doses of AVP in SHR in spite of suppressed reflex bradycardia. It is suggested that the peripheral action of AVP on the vascular system is attenuated in SHR.     

Enhanced catabolism to acetaldehyde in rostral ventrolateral medullary neurons accounts for the pressor effect of ethanol in spontaneously hypertensive rats

We have previously shown that ethanol microinjection into the rostral ventrolateral medulla (RVLM) elicits sympathoexcitation and hypertension in conscious spontaneously hypertensive rats (SHRs) but not in Wistar-Kyoto (WKY) rats. In this study, evidence was sought to implicate the oxidative breakdown of ethanol in this strain-dependent hypertensive action of ethanol. Biochemical experiments revealed significantly higher catalase activity and similar aldehyde dehydrogenase (ALDH) activity in the RVLM of SHRs compared with WKY rats. We also investigated the influence of pharmacological inhibition of catalase (3-aminotriazole) or ALDH (cyanamide) on the cardiovascular effects of intra-RVLM ethanol or its metabolic product acetaldehyde in conscious rats. Compared with vehicle, ethanol (10 μg/rat) elicited a significant increase in blood pressure in SHRs that lasted for the 60-min observation period but had no effect on blood pressure in WKY rats. The first oxidation product, acetaldehyde, played a critical role in ethanol-evoked hypertension because 1) catalase inhibition (3-aminotriazole treatment) virtually abolished the ethanol-evoked pressor response in SHRs, 2) intra-RVLM acetaldehyde (2 μg/rat) reproduced the strain-dependent hypertensive effect of intra-RVLM ethanol, and 3) ALDH inhibition (cyanamide treatment) uncovered a pressor response to intra-RVLM acetaldehyde in WKY rats similar to the response observed in SHRs. These findings support the hypothesis that local production of acetaldehyde, due to enhanced catalase activity, in the RVLM mediates the ethanol-evoked pressor response in SHRs.     

Sympathoinhibition from ventrolateral periaqueductal gray mediated by 5-HT(1A) receptors in the RVLM

The role of 5-hydroxytryptamine 1A (5-HT(1A)) receptors located in the rostral ventrolateral medulla (RVLM) in the mediation of a sympathoinhibitory and depressor response elicited from the ventrolateral periaqueductal gray (vlPAG) matter of the midbrain was examined in pentobarbital sodium-anesthetized rats. Activation of neurons in the vlPAG evoked a decrease in renal and lumbar sympathetic nerve activities and a decrease in arterial blood pressure. After microinjection of the specific 5-HT(1A)-receptor antagonist WAY-100635 into the pressor area of the RVLM, the vlPAG-evoked sympathoinhibition and hypotension was attenuated to control levels (7 of 15 animals) or converted into a sympathoexcitation and pressor response (8 of 15 animals). Baroreflex inhibition of sympathetic nerve activity was not impaired by microinjection of WAY into the sympathoexcitatory region of the RVLM. These data suggest that sympathoinhibition and hypotension elicited by activation of neurons in the vlPAG are mediated by 5-HT(1A) receptors in the RVLM.     

Skeletal muscle reflex-mediated changes in sympathetic nerve activity are abnormal in spontaneously hypertensive rats

In hypertension, the blood pressure response to exercise is exaggerated. We demonstrated previously that this heightened pressor response to physical activity is mediated by an overactive skeletal muscle exercise pressor reflex (EPR), with important contributions from its metaboreflex and mechanoreflex components. However, the mechanisms driving the abnormal blood pressure response to EPR activation are largely unknown. Recent evidence in humans suggests that the muscle metaboreflex partially mediates the enhanced EPR-induced pressor response via abnormally large changes in sympathetic nerve activity (SNA). Whether the muscle mechanoreflex induces similarly exaggerated alterations in SNA in hypertension remains unknown, as does the role of the mechanoreceptors mediating muscle reflex activity. To address these issues, the EPR was selectively activated by electrically inducing hindlimb muscle contraction in decerebrate normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Stimulation of the EPR evoked significantly larger increases in mean arterial pressure (MAP) and renal SNA (RSNA) in SHR compared with WKY (ΔRSNA from baseline: 140 ± 11 vs. 48 ± 8%). The mechanoreflex was stimulated by stretching hindlimb muscle which likewise elicited significantly greater elevations in MAP and RSNA in SHR than WKY (ΔRSNA from baseline: 105 ± 11 vs. 35 ± 7%). Blockade of mechanoreceptors in muscle with gadolinium significantly attenuated the MAP and RSNA responses to contraction and stretch in SHR. These data suggest that 1) the exaggerated pressor response to activation of the EPR and muscle mechanoreflex in hypertension is mediated by abnormally large reflex-induced augmentations in SNA and 2) this accentuated sympathetic responsiveness is evoked, in part, by stimulation of muscle mechanoreceptors.     

Endothelin-1 in hypertension in the baroreflex-intact SHR: a role independent from vasopressin release

This study sought to identify whether central endothelin (ET) receptor activation contributes to the elevated pressure in spontaneously hypertensive rats (SHR) and whether an ET-stimulated vasopressin (AVP) release mediates the increased pressure. In Wistar Kyoto (WKY) rats, intracerebroventricular ET-1 induced a dose-dependent pressor response that was shifted rightward in SHR. ET(A) antagonism decreased mean arterial pressure in baroreflex-intact SHR (P<0.01), consistent with inhibition of endogenous ET-1, and blocked the pressor response to exogenous ET-1 in both strains. ET-1 increased AVP only after sinoaortic denervation (P<0.05). Contrary to WKY, sinoaortic denervation was required to elicit a significant pressor response with 5 pmol ET-1 in SHR. Sinoaortic denervation permitted ET-1 to increase AVP in both strains, and peripheral V(1) blockade decreased pressure in denervated but not intact rats. After nitroprusside normalized pressure in SHR, the pressor and AVP secretory responses paralleled those in WKY. Thus endogenous ET(A) receptor mechanisms contribute to hypertension, independent of AVP, in baroreflex-intact SHR. Although blunted in the hypertensive state, the arterial baroreflex buffers the ET-1-induced pressor and AVP secretory responses in both strains.     

Blood pressure responsiveness during the development of hypertension in the conscious spontaneously hypertensive rat

Blood pressure responsiveness to iv noradrenaline and angiotensin II was studied in conscious, freely moving, age-matched spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats from 4 to 16 weeks of age. At 4 and 6 weeks the SHR showed small, but nonsignificant increases in responsiveness compared with WKY to both noradrenaline and angiotensin II. At 8 weeks they exhibited similar responses to the WKY. Subsequently, at 12 and 16 weeks decreased responsiveness to noradrenaline (nonsignificant) and angiotensin II (p less than 0.05 at 12 and 16 weeks) was observed in SHR versus WKY. At 16 weeks of age, hexamethonium caused potentiation of the blood pressure response to noradrenaline and angiotensin II, but to the same degree in the two strains. Captopril at this age did not elicit potentiation to noradrenaline or angiotensin II in either strain. These results indicate that there is no rise in blood pressure responsiveness to circulating pressor agents, parallel to the development of hypertension in SHR. Increased receptor occupancy or more active attenuating reflexes in SHR versus WKY appear not to be involved in the absence of hyperresponsiveness in intact conscious SHR at 16 weeks of age.     

The role of neurons of the caudal ventrolateral region of the medulla oblongata of cats in the mechanism of realization of the cardio-hemodynamic reaction

Glycine injection to the identified area of the RVLM leads to the development of a characteristic depressor reaction, due to a decrease of the total peripheral vascular resistance (TRP). Glycine injection to the identified area of CVLM results in the developing pressor reaction also due to the changes of TRP. Glycine injection to CVLM under preliminary functional switch-off the RVLM neuronal activity is not accompanied by the development of pressor reaction. This can be an evidence that CVLM sympathoinhibitory neurones act on cardiohemodynamics by their interaction with RVLM sympathoexcitatory neurones. Turn off of the tonically active sympathoinhibitory CVLM neurones does not affect the character of the reactions depending on the inhibition or excitation of sympathoexcitatory RVLM neurones.     

Catestatin in rat RVLM is sympathoexcitatory, increases barosensitivity, and attenuates chemosensitivity and the somatosympathetic reflex

The fundamental role and corollary effects of neuropeptides that govern cardiorespiratory control in the brain stem are poorly understood. One such regulatory peptide, catestatin [Cts, human chromogranin A-(352-372)], noncompetitively inhibits nicotinic-cholinergic-stimulated catecholamine release. Previously, we demonstrated the presence of chromogranin A mRNA in brain stem neurons that are important for the maintenance of arterial pressure. In the present study, using immunofluorescence histochemistry, we show that Cts immunoreactivity is colocalized with tyrosine hydroxylase in C1 neurons of the rostral ventrolateral medulla (RVLM, n = 3). Furthermore, we investigated the effects of Cts on resting blood pressure, splanchnic sympathetic nerve activity, phrenic nerve activity, heart rate, and adaptive reflexes. Cts (1 mM in 50 nl or 100 μM in 50-100 nl) was microinjected into the RVLM in urethane-anesthetized, vagotomized, ventilated Sprague-Dawley rats (n = 19). Cardiovascular responses to stimulation of carotid baroreceptors, peripheral chemoreceptors, and the sciatic nerve (somatosympathetic reflex) were analyzed. Cts (1 mM in 50 nl) increased resting arterial pressure (28 ± 3 mmHg at 2 min postinjection), sympathetic nerve activity (15 ± 3% at 2 min postinjection), and phrenic discharge amplitude (31 ± 4% at 10 min postinjection). Cts increased sympathetic barosensitivity 40% (slope increased from -0.05 ± 0.01 before Cts to -0.07 ± 0.01 after Cts) and attenuated the somatosympathetic reflex [1st peak: 36% (from 132 ± 32.1 to 84.0 ± 17.0 μV); 2nd peak: 44% (from 65.1 ± 21.4 to 36.6 ± 14.1 μV)] and chemoreflex (blood pressure response to anoxia decreased 55%, sympathetic response decreased 46%). The results suggest that Cts activates sympathoexcitatory bulbospinal neurons in the RVLM and plays an important regulatory role in adaptive reflexes.     

The characteristics of shuttle avoidance learning in spontaneously hypertensive and normotensive rats]

In spontaneously hypertensive (strain SHR) and normotensive (strain WKY) rats was studied the elaboration of conditioned reflex of active avoidance in shuttle box. In case when the shuttle box was divided by a partition the SHR rats learned worse than WKY rats. In shuttle chamber without partition the SHR rats, on the contrary, learned better that WKY ones. Such character of interlinear differences can be connected with properties of formation of the instrumental habit of deliverance from electropainful stimulus, because the presence of partition significantly hampered its fulfillment. The obtained results, compared with literature data, testify to the fact that differences of SHR and WKY rats in elaboration of conditioned reflexes are explained basically by the properties of their unconditioned activity and not of the associative processes.     

Dysfunction of supramedullary alpha-adrenergic mechanisms following sino-aortic denervation in Kyoto Wistar rats

Central α-adrenergic mechanisms of blood pressure regulation were investigated by injecting norepinephrine or bradykinin into the carotid input of the cross-circulated head preparations of normotensive Wistar Kyoto rats (WKY). Rats were divided into three groups: sham-operated (sham), carotid sinuses denervated (SD) and carotid sinuses and aortic nerves debuffered (SAD). Norepinephrine, 5 μg, produced vasodepression in all rats, accompanied by corresponding decreases in sympathetic nerve activity recorded in some rats. Magnitude of vasodepression was largest in SAD rats. In sham rats, bradykinin, 1 μg, produced a biphasic response:initial vasodepression followed by a sustained pressor phase. This was accompanied by corresponding changes in peripheral sympathetic nerve activity recorded in some rats. In both SAD and SD rats bradykinin-induced vasodepression was abolished, while the magnitude of the pressor phase became more prominent. The increase in the pressor phase was greater in SAD than in SD rats. In similar studies of spontaneously hypertensive rats (SHR), responses to both α-adrenergic agonist and bradykinin are augmented, suggesting a dysfunction of hypothalamic α-adrenergic mechanisms. Since in the present study it has been shown that sino-aortic denervation produces effects similar to those seen in SHR, dysfunction of buffer nerves may account for the deficient central α-adrenergic mechanisms in SHR.     

Exaggerated natriuresis in experimental hypertension

The exaggerated natriuretic response to intravenous isotonic saline volume expansion in conscious spontaneous hypertensive rats (SHR), compared to normotensive Wistar-Kyoto rats (WKY), is associated with an exaggerated inhibition of renal nerve activity. Following bilateral renal denervation, the natriuresis was significantly attenuated in SHR but unaffected in WKY. Thus, the exaggerated natriuretic response to intravenous isotonic saline in SHR is dependent on their enhanced inhibition of renal nerve activity. Conscious Dahl salt-sensitive rats, on either low or high salt diet, did not exhibit an exaggerated natriuretic response to intravenous isotonic saline volume expansion which may be explained by their known impairment of cardiopulmonary baroreceptor reflex mediated suppression of efferent sympathetic nerve activity during intravenous volume expansion. Conscious hypertensive DOCA-NaCl rats exhibited an exaggerated natriuretic response to oral but not to intravenous isotonic saline volume expansion, suggesting differences in gastrointestinal absorption of isotonic saline. It is concluded that enhanced inhibition of efferent renal sympathetic nerve activity via cardiopulmonary baroreceptor reflex activation contributes to the exaggerated natriuretic response to intravenous isotonic saline volume expansion in certain models of experimental hypertension.     

Effects of angiotensin II on the spontaneous activity of rostral ventrolateral medullary cardiovascular neurons and blood pressure in spontaneously hypertensive rats

The interactive role of rostral ventrolateral medulla (RVL) cardiovascular neurons and brain angiotensin II (Ang II) in regulating the arterial blood pressure was examined by recording simultaneously the spontaneous activity of these spinal projecting neurons and the arterial blood pressure in the pentobarbital-anesthetized spontaneously hypertensive rat (SHR) and its normotensive control, the Wistar Kyoto rat (WKY). It was found that Ang II elicited dose-dependent excitatory responses in a subpopulation of RVL cardiovascular neurons, followed by a subsequent increase in blood pressure. These effects of Ang II were significantly greater in SHR than in WKY. The effects were attenuated or abolished by co-administration of Ang II antagonist, [Sar¹, Ile⁸]-Ang II. Pre-administration of [Sar¹, Ile⁸]-Ang II to RVL using bilateral microinjection attenuated the blood pressure effects of intracerebroventricularly administered Ang II by as much as 70%. These results indicated that spinal projecting RVL cardiovascular neurons are important in mediating the pressor action of Ang II. The enhanced sensitivity and responsiveness of RVL cardiovascular neurons to Ang II may be pertinent to the genesis of hypertension in adult SHR.