Intermittent activation of peripheral chemoreceptors in awake rats induces Fos expression in rostral ventrolateral medulla-projecting neurons in the paraventricular nucleus of the hypothalamus.

Despite the well-established sympathoexcitation evoked by chemoreflex activation, the specific sub-regions of the CNS underlying such sympathetic responses remain to be fully characterized. In the present study we examined the effects of intermittent chemoreflex activation in awake rats on Fos-immunoreactivity (Fos-ir) in various subnuclei of the paraventricular nucleus of the hypothalamus (PVN), as well as in identified neurosecretory preautonomic PVN neurons. In response to intermittent chemoreflex activation, a significant increase in the number of Fos-ir cells was found in autonomic-related PVN subnuclei, including the posterior parvocellular, ventromedial parvocellular and dorsal-cap, but not in the neurosecretory magnocellular-containing lateral magnocellular subnucleus. No changes in Fos-ir following chemoreflex activation were observed in the anterior PVN subnucleus. Experiments combining Fos immunohistochemistry and neuronal tract tracing techniques showed a significant increase in Fos-ir in rostral ventrolateral medulla (RVLM)-projecting (PVN-RVLM), but not in nucleus of solitarii tract (NTS)-projecting PVN neurons. In summary, our results support the involvement of the PVN in the central neuronal circuitry activated in response to chemoreflex activation, and indicate that PVN-RVLM neurons constitute a neuronal substrate contributing to the sympathoexcitatory component of the chemoreflex.

Effect of nucleus ambiguus lesion on the development of neurogenic hypertension.

These studies evaluated the role of the nucleus ambiguus in regulating heart rate and cardiovascular activity. Three days after lesion of the nucleus ambiguus, arterial pressure and heart rate were unchanged; however, subsequent sinoaortic deafferentation produced a significantly greater increase of pressure (156 +/- 4 vs 124 +/- 6 mm Hg) compared to sham lesion. In both groups the heart rate was increased after deafferentation and the intrinsic heart rate (rate seen after autonomic blockade with atropine and propranolol) was significantly reduced. When the sequence was reversed (deafferentation before lesion), pressure (126 +/- 6 vs 126 +/- 7 mm Hg) and heart rate (334 +/- 17 and 340 +/- 16 beats/min) were not altered; however, intrinsic rate fell more. When the nucleus ambiguus was stimulated electrically, two responses emerged: increased pressure without rate changes and increased pressure with bradycardia. These data indicate that 1) lesion of the nucleus ambiguus facilitates hypertension produced by sinoaortic deafferentation unless lesioning follows deafferentation; and 2) stimulation of the nucleus ambiguus produces a pressor effect that is independent of the bradycardic response. We conclude that the nucleus ambiguus may be related to autonomic control of both heart rate and arterial pressure.

Role of the nucleus ambiguus in the regulation of heart rate and arterial pressure.

The present study examined the effect of lesion of cell bodies in the nucleus ambiguus area on the development of neurogenic hypertension and further explored the cardiovascular responses produced by chemical and electrical stimulation of the nucleus ambiguus and the neighboring C1 region. Three days after chemical lesion of the nucleus ambiguus with kainic acid, arterial pressure and heart rate were unchanged; however, subsequent sinoaortic deafferentation produced a significantly greater increase of arterial pressure (157 +/- 7 vs 132 +/- 5 mm Hg) and heart rate (436 +/- 10 vs 374 +/- 10 beats/min) compared with those produced by sham lesion. Glutamate injected into the nucleus ambiguus increased arterial pressure and heart rate at 20 nmol/100 nl and decreased heart rate at 50 nmol/100 nl. Glutamate injected into the C1 area increased arterial pressure and heart rate at both doses. Gamma-Aminobutyric acid at 50 nmol/100 nl produced bradycardia and a fall in arterial pressure when injected into both the nucleus ambiguus and C1 area. The heart rate responses to gamma-aminobutyric acid and glutamate were attenuated in sinoaortic-deafferentated rats. The nucleus ambiguus and the C1 region were mapped using electrical stimulation with microelectrodes. All points stimulated in three anteroposterior sections in the nucleus ambiguus and the C1 area produced increases in arterial pressure, whereas bradycardia was restricted to the middle of three lateral coordinates associated with the center of the nucleus ambiguus and the C1 area ventral to the nucleus ambiguus.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of selective denervation of baroreceptors on pulmonary ventilation and arterial pressure lability in rat.

Earlier studies report that sinoaortic baroreceptor denervation (SAD) in rats causes moderate elevation of mean arterial pressure along with a marked increase of arterial pressure lability (APL). In this context, we studied the effects of selective aortic denervation (AD) or selective carotid denervation (CD) on the regulation of blood pressure. In addition, we evaluated the effects of selective or total baroreceptor denervation on pulmonary ventilation and ventilation-related changes of arterial pressure. Mean arterial pressure was evaluated by computer-assisted techniques, and ventilation was measured by whole body plethysmography on conscious freely moving rats. With this approach, equal increases of mean arterial pressure were obtained for rats that had undergone AD, CD, and SAD. The APL was higher in SAD rats than in selectively denervated rats. CD and AD rats had an elevated APL relative to sham-operated animals, and its increase was approximately equal for the two selectively denervated groups. Total as well as selective denervation had relatively small effects on ventilation and on the general pattern of breathing. In all groups, this pattern consisted of regular ventilation, periodically interrupted by single deeper breaths. In SAD, AD, and CD animals, these larger tidal volumes were associated with marked transient reductions of mean arterial pressure, whereas small decreases of pressure occurred in sham-operated rats. The results indicate that both groups of baroreceptors must be present to keep mean arterial pressure at its normal level. Moreover, both receptor groups are equally important in reducing APL. Ventilation contributes to generation of APL after total or selective baroreceptor removal. Such ventilation-induced pressure changes are kept at a minimum in baroreceptor-intact rats.

Tachycardic responses during the development of renal hypertension.

Basal heart rate (HR) of conscious rats under resting conditions was measured daily by electrocardiogram (ECG) during the development of one-kidney, one clip (1K1C) hypertension. A progressive increase in HR (mean +/- SEM) was observed from Day 1 to 7: 318 +/- 11; 330 +/- 18, 338 +/- 18; 344 +/- 19; 372 +/- 14; 374 +/- 11, and 388 +/- 12 bpm, respectively. During the same period, mean arterial pressure (MAP) also increase progressively: 126 +/- 2; 129 +/- 2; 134 +/- 4; 135 +/- 7; 144 +/- 2 and 157 +/- 4 mm Hg, respectively. From Day 7 onward, the HR declined, reaching values of 336 +/- 13 bpm on Day 9, with no further alterations for the next 21 days. The MAP continued to rise, however, being 158 +/- 4 on Day 8 and 175 +/- 7 mm Hg on Day 30. Sham-operated rats showed no changes in HR or MAP. During the development of hypertension, blockade of converting enzyme with captopril (10 mg/kg, i.v.) caused a significant blood pressure fall on Day 1 (-27 +/- 1 mm Hg) and Day 3 (-18 +/- 2 mm Hg), whereas on Day 6 (-9 +/- 3 mm Hg) and Day 14 (-8 +/- 3 mm Hg) the fall was not different from that of the normotensive control rats (NCR) (-6 +/- 1 mm Hg). Reflex bradycardia, produced by increasing doses of phenylephrine which elevated the MAP by 10 to 40 mm Hg, was studied in conscious NCR and renal hypertensive rats (RHR) 3 and 7 days after surgery during the development of renal hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical renal medullectomy and arterial pressure response to sinoaortic denervation.

We investigated in conscious Wistar-Kyoto rats the effect of chemical renal medullectomy on the responses of mean arterial pressure, arterial pressure lability, and heart rate to sinoaortic deafferentation (SAD). Chemical medullectomy was obtained by the intravenous administration of 2-bromoethylamine hydrobromide (2-BEA) 2-3 weeks before SAD or sham SAD. Chemically medullectomized rats were compared with control rats treated with saline. In control rats, the increase in mean arterial pressure elicited by SAD was not significantly greater than that produced by sham SAD. In medullectomized rats, SAD significantly increased mean arterial pressure compared with sham SAD. No direct relation was observed between the response of mean arterial pressure to SAD and the grade (1, 2, or 3) of lesion of the renal papilla. In control rats, SAD increased significantly arterial pressure lability. Chemical medullectomy did not affect basal lability or the increased lability after SAD. No direct relation was observed between increased arterial pressure lability due to SAD and the grade of lesion of the renal papilla. SAD produced a conspicuous tachycardia in control rats. Chemical medullectomy did not affect basal heart rate or the tachycardia produced by SAD. No direct relation was observed between the extent of this tachycardia and the grade of lesion of the renal papilla. These data indicate that lesions of the renal papilla lead to a significant increase in mean arterial pressure after SAD, without affecting basal pressure or heart rate. In addition, SAD per se did not increase significantly the mean arterial pressure in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in vascular resistance during carotid occlusion in normal and baroreceptor-denervated rats.

In the present study, we investigated changes in mesenteric, renal, and hindquarter vascular resistance during the pressor response produced by bilateral carotid occlusion (BCO) in conscious, freely moving normal and denervated (aortic, carotid, or both) rats. BCO was performed using special previously implanted cuffs. In control normal rats, the increase in mean arterial pressure (MAP) during early and late responses (37 +/- 4 and 21 +/- 2 mm Hg, respectively) was related to increased renal (125 +/- 12% and 45 +/- 10%) and mesenteric (38 +/- 13% and 41 +/- 5%) but not hindquarter (14 +/- 4% and 8 +/- 7%) vascular resistance. In aortic-denervated rats, the greater MAP increase in early and late responses (57 +/- 4 and 44 +/- 4 mm Hg, respectively) compared with normal rats was related to a marked increase in hindquarter (137 +/- 26% and 106 +/- 26%) and mesenteric (104 +/- 14% and 66 +/- 9%) vascular resistance. In carotid-denervated rats, MAP increase and change in vascular resistance were similar to those values observed in control rats. Sinoaortic-denervated rats showed a greater MAP increase (34 +/- 4 mm Hg) during late response and a reduced increase in renal vascular resistance (46 +/- 6%) during early response.(ABSTRACT TRUNCATED AT 250 WORDS)

Bradycardic responses to microinjection of N-methyl-D-aspartate into the nucleus tractus solitarius are inhibited by local activation of 5-HT(3) receptors.

Previous reports have described that glutamate ionotropic receptors in the nucleus tractus solitarius (NTS) are involved in the reflex control of heart rate, and that such a control can be inhibited by NTS-5-HT(3) receptor stimulation. In the present study, we examined in urethane anaesthetized rats the effects of intra-NTS microinjection of 1-(m-chlorophenyl)-biguanide (CPBG), a potent and selective 5-HT(3) receptor agonist, on the cardiovascular responses to local administration of glutamate ionotropic receptor agonists. Intra-NTS microinjection of CPBG reduced the atropine-sensitive bradycardia elicited by local microinjection of NMDA without affecting the cardiovascular responses to intra-NTS microinjections of AMPA or kainic acid. The reduction by CPBG of the NMDA-evoked cardiac response was blocked by prior intra-NTS microinjection of granisetron, a 5-HT(3) receptor antagonist, as well as bicuculline, a GABA(A) receptor antagonist. These results suggest that the stimulation of NTS 5-HT(3) receptors specifically reduces, via a GABA-dependent mechanism, the cardiac response to local NMDA administration.

Changes of the intrinsic heart rate during the onset of renal hypertension.

Intrinsic heart rate (IHR) measured after autonomic blockade with atropine and propranolol in conscious one-kidney, one clip (1-K,1C) hypertensive rats was increased and associated with the peak of tachycardia that occurs 7 days after clipping. No significant changes in basal or intrinsic heart rate were observed 3 or 14 days after clipping. The effect of exogenous angiotensin II (ANG II) was compared to that of norepinephrine (NOR) and isoproterenol (ISO) in conscious normotensive rats. Infusion of ANG II for 3 h induced a slight increase in heart rate which was accompanied by a larger increase in IHR. In contrast, the infusion of NOR or ISO induced intense tachycardia without affecting IHR. The intense tachycardia observed in conscious rats 48 h after sinoaortic denervation, was not accompanied by changes in IHR. Furthermore, the adrenergic stimulation produced by infusion of either NOR or ISO or that occurring after 48 h of sinoaortic denervation, did not modify IHR in conscious rats, whereas a 3-h infusion of ANG II did. These data suggest that the tachycardia observed in rats during the onset of 1-K,1C hypertension may be partly due to increased IHR caused by ANG II.

Tachycardia during reversal of one-kidney, one-clip hypertension in conscious rats.

The efferent sympathetic activity of the heart was investigated during reversal of one-kidney, one-clip (1K,1C) hypertension in conscious, freely moving rats using changes in heart rate as an index. One-kidney, one-clip hypertensive rats presented marked tachycardia during the first 8 h after unclipping. Mean arterial pressure fell 28% 3 h after unclipping and 37% 8 h after unclipping. In a separate experiment, short term infusion (15 min) of sodium nitroprusside in conscious freely moving rats produced similar tachycardia in hypertensive and sham-operated rats. The present results indicate that the baroreceptor reflex of the heart was operating normally during the prompt reversal of hypertension after unclipping.

Neurotransmission of the cardiovascular reflexes in the nucleus tractus solitarii of awake rats.

Chemoreflex activation with potassium cyanide (i.v.) produces pressor and bradycardic responses in awake rats. Microinjection of AP-5, a selective NMDA receptor antagonist, into the nucleus tractus solitarii (NTS) produced a dose-dependent blockade of the bradycardic response; while microinjection of DNQX, a selective non-NMDA receptor antagonist, or kynurenic acid, a nonselective ionotropic receptor antagonist, produced only a partial reduction in the pressor response, indicating that the bradycardic component of the chemoreflex is mediated by NMDA receptors and that the sympathoexcitatory component may involve neurotransmitters other than excitatory amino acids. With respect to the baroreflex, we verified that the gain of baroreflex bradycardia in response to phenyleprine (Phe) infusion was significantly reduced in a dose-dependent manner by microinjection of AP-5 into the NTS, indicating that the parasympathetic component of the baroreflex is mediated mainly by NMDA receptors. However, in a series of experiments involving the electrical stimulation of the aortic depressor nerve (ADN) we observed that the maximal bradycardic response was almost blocked by the combination of microinjection of NMDA and non-NMDA receptor antagonists into the NTS, while the depressor response was only partially reduced. These data indicate that the bradycardic response produced by the activation of the baroreflex with Phe is mediated by mechanisms differing from those in response to the electrical stimulation of the ADN because phenylephrine also activates carotid and aortic baroreceptors, while unilateral electrical stimulation of the ADN involves only one specific set of baroreceptor afferents. These data also indicate that the sympatho inhibitory component of this response may involve neurotransmitters other than L-glutamate. We discuss the possibility that two different afferent systems of arterial baroreceptors are involved in the modulation of parasympathoexcitation and sympathoinhibition: one activated within the normal range of pulsatile arterial pressure (on a pulse-to-pulse basis) and the other acting under circumstances of challenge to the pulsatile arterial pressure above the normal range.

Transient changes in blood pressure during spontaneous deep breaths in rats with sinoaortic deafferentation.

Sinoaortic deafferentation (SAD) in rats produces moderate increases in mean arterial pressure (MAP) along with a large augmentation of arterial pressure lability (APL). The mechanisms generating this APL are incompletely understood. To study the possible influence of breathing activity on APL in conscious SAD rats, we simultaneously recorded pulmonary ventilation and arterial blood pressure. The general pattern of pulmonary ventilation was the same in normal, sham-operated, and SAD rats. In all groups single large tidal volumes were regularly interposed in 1- to 2-min periods of shallower breathing. In SAD rats these single large inspirations were consistently accompanied by substantial and abrupt reductions of MAP, whereas this effect was markedly smaller or absent in normal and sham-operated rats. The data reflect the lack of fast moment-to-moment control of arterial pressure normally exerted by the aortic and carotid baroreceptors. In this context, effects of ventilatory changes must be considered along with humoral and neurogenic factors to explain APL after SAD.

Microinjection of L-glutamate into the nucleus tractus solitarii increases arterial pressure in conscious rats.

Microinjection of L-glutamate into the nucleus tractus solitarii (NTS) of anesthetized rats produces a fall in mean arterial pressure (MAP) similar to that observed during activation of baroreceptor afferents. In the present study we examined the effect of bilateral microinjections of L-glutamate through chronically implanted cannulae in the NTS of conscious freely moving rats. Group I (n = 6) was studied under conscious conditions and 24 h later the rats were anesthetized with urethane and the effects of L-glutamate re-examined. In conscious rats, L-glutamate (30 pmol to 5 nmol/100 nl) produced dose-dependent increases in MAP (+37 +/- 7 mmHg, 5 nmol), whereas under urethane anesthesia falls in MAP were observed (-11 +/- 3 mmHg, 5 nmol). Group II (n = 7) was studied under conscious conditions and 1 h later the rats were anesthetized with chloralose and the effects of L-glutamate re-examined. In this group of conscious rats L-glutamate (300 pmol to 5 nmol/100 nl) also produced dose-dependent increases in MAP (+37 +/- 5 mmHg, 5 nmol), whereas under chloralose anesthesia a dose-dependent depressor response was observed (-33 +/- 6 mmHg, 5 nmol). Saline microinjections into the NTS of conscious and anesthetized rats produced negligible effects. These data demonstrate that microinjection of L-glutamate into the NTS of rats produces a pressor response in conscious animals in contrast to depressor responses in animals anesthetized with chloralose or urethane.(ABSTRACT TRUNCATED AT 250 WORDS)

Microinjection of NMDA antagonist into the NTS of conscious rats blocks the Bezold-Jarisch reflex.

The purpose of the present study was to evaluate whether or not cardiovagal excitatory and sympatho-inhibitory pathways of the Bezold-Jarisch reflex at the NTS level were mediated by NMDA receptors. The Bezold-Jarisch reflex was activated by intravenous (i.v.) injection of serotonin in conscious rats before and after microinjection of phosphonovaleric acid (AP-5) a selective NMDA antagonist, into the NTS. The Bezold-Jarisch reflex was also activated before and after methyl-atropine (i.v.) in order to evaluate if the changes in mean arterial pressure were dependent on the bradycardic response. The data showed that AP-5 into the NTS produced a dose-dependent reduction in both bradycardic and hypotensive responses to activation of the Bezold-Jarisch reflex. Methyl-atropine also blocked the bradycardic and hypotensive responses to Bezold-Jarisch reflex activation. The data show that in conscious rats the cardiovagal component of the Bezold-Jarisch reflex plays a major role in the cardiovascular changes produced by the activation of this reflex and suggest that the neurotransmission of the cardiovagal component of the Bezold-Jarisch reflex is mediated by NMDA receptors.

NMDA receptor antagonist blocks the bradycardic but not the pressor response to L-glutamate microinjected into the nucleus tractus solitarius (NTS) of unanesthetized rats.

In the present study we evaluated the role of NMDA receptors on the pressor and bradycardic responses to L-glutamate (L-Glu) microinjected into the nucleus tractus solitarius (NTS) of unanesthetized rats. L-Glu (1 nmol/100 nl) was microinjected into the NTS before and 10 min after microinjection of phosponovaleric acid (AP-5), a selective NMDA receptor antagonist, into the NTS of three different groups of rats (0.5, 2.0 and 10.0 nmol/100 nl). Microinjection of AP-5 into the NTS produced a dose-dependent reduction in the bradycardic response to L-Glu. However, no significant change in the pressor response to L-Glu was observed. These results indicate that the activation of the cardiovagal component (bradycardia) by L-Glu involves NMDA receptors and suggest that the activation of the sympatho-excitatory component (pressor response) by L-Glu in the commissural NTS is mediated by non-NMDA receptors.

Bradycardic and hypotensive responses to microinjection of L-glutamate into the lateral aspect of the commissural NTS are blocked by an NMDA receptor antagonist.

Baroreflex activation by phenylephrine infusion produces a bradycardic response while microinjection of L-glutamate into the most lateral aspect of the commissural nucleus tractus solitarius (NTS, 0.8 mm lateral to the midline) produces bradycardic and hypotensive responses. In the present study we investigated the role of NMDA receptors in the lateral aspect of the commissural NTS (0.8 mm lateral to the midline) in the bradycardic and hypotensive responses to microinjection of L-glutamate as well as in the processing of the bradycardic response to the baroreflex activation. The hypotensive and bradycardic responses to L-glutamate microinjection into the NTS were blocked by methyl-atropine (intravenous, i.v.), indicating that the hypotensive response was secondary to the bradycardia. Microinjection of L-glutamate (1 nmol/50 nl) into the NTS was performed before and after microinjection of increasing doses of phosphonovaleric acid (AP-5, a selective NMDA antagonist) at the same site. The microinjection of AP-5 [0.5 (n = 9), 2.0 (n = 8) and 10.0 nmol/50 nl (n = 7)] into the NTS (0.8 mm lateral to the midline) produced a dose-dependent blockade of the bradycardic and hypotensive responses to L-glutamate. In a specific group of rats the microinjection of 10 nmol/50 nl of AP-5 produced a significant reduction in baroreflex sensitivity 2 min after microinjection into the lateral NTS [gain = -1.48 +/- 0.12 vs. -0.5 +/- 0.2 beats/mmHg, (n = 5)], which was reversible. The data show that the bradycardic responses produced by microinjection of L-glutamate into the most lateral aspect of the commissural NTS or by activation of the baroreflex were blocked by microinjection of AP-5, indicating that the neurotransmission of the parasympathetic component of the baroreflex in the neurons of the lateral aspect of the commissural NTS involves NMDA receptors.

Neurotransmission of the Bezold-Jarisch reflex in the nucleus tractus solitarii of sino-aortic deafferentated rats.

The Bezold-Jarisch (B-J) reflex was activated by serotonin (5-HT, i.v.) before and 10 min after bilateral microinjection of increasing doses of kynurenic acid, a non-selective antagonist of excitatory amino acid (EAA) receptors, into the commissural nucleus tractus solitarii (NTS) of sino-aortic deafferentated (SAD) and sham-operated (SO) unanesthetized rats. Increasing doses of kynurenic acid produced a dose-dependent blockade of the bradycardic and hypotensive responses to B-J reflex activation in both SO (from 0.1 to 10.0 nmol/100 nl) and SAD (from 0.1 to 2.0 nmol/100 nl). Comparison of the effect of kynurenic acid on the hypotension and bradycardic dose-response curves showed a significant difference between SO and SAD rats, indicating that smaller doses of kynurenic acid are required in SAD rats than in SO rats to block the neurotransmission of the B-J reflex in the NTS. The data also showed that bilateral microinjection of kynurenic acid into the NTS at doses of 0.5 (131 +/- 7 vs. 115 +/- 8 mmHg) and 2.0 nmol/100 nl (140 +/- 11 vs. 116 +/- 9 mmHg) produced an acute and significant increase in the basal mean arterial pressure of SAD rats similar to that observed with the same doses in SO rats, which was back to control values 5-10 min later. The increase in basal mean arterial pressure immediately after kynurenic acid microinjection into the NTS of SAD rats suggests that in the absence of the arterial baroreceptors, the B-J reflex plays an important role in the autonomic regulation of the circulation. The data also show different dose-response curves for hypotension and bradycardia in response to B-J reflex activation in SAD than in SO rats in the presence of increasing doses of kynurenic acid into the NTS, indicating that the neurotransmission of the B-J reflex in the NTS of SAD rats is more sensitive to the blockade of the EAA receptors than in SO rats.

Involvement of the paraventricular nucleus of the hypothalamus in the pressor response to chemoreflex activation in awake rats.

Chemoreflex activation with potassium cyanide (KCN, i.v.) produces pressor and bradycardic responses in awake rats in addition to the tachypneic response. In the present study we evaluated the role of the paraventricular nucleus of the hypothalamus (PVN) in the cardiovascular responses to chemoreflex activation in awake rats. Bilateral electrolytic lesion of the PVN was performed 1 day before chemoreflex activation and the results were compared to those obtained with sham-lesioned rats. Bilateral electrolytic lesion of the PVN (n=6) produced a significant reduction in both the magnitude (+51+/-5 vs. +22+/-2 mmHg) and duration (+26+/-5 vs. +6+/-2 s) of the pressor response to chemoreflex activation when compared to sham-lesioned rats (n=10). The bradycardic response to chemoreflex activation in rats with bilateral lesion of the PVN was not significantly different from the response of sham-lesioned rats (-229+/-20 vs. -88+/-76 bpm). Unilateral or partial bilateral lesion of the PVN (n=10) produced no significant changes in the pressor response (+51+/-5 vs. +49+/-3 mmHg), in the duration of the response (+26+/-5 vs. +18+/-3 s) or in the bradycardic response (-229+/-20 vs. -230+/-27 bpm) compared to sham-lesioned rats. The data show that effective bilateral lesion of the PVN produced a significant reduction in the magnitude and duration of the pressor response, indicating that the PVN plays a key role in the processing of the sympathoexcitatory component of the chemoreflex.

Tachycardia during the onset of one-kidney, one-clip renal hypertension: role of the renin-angiotensin system and AV3V tissue.

We have previously demonstrated a transitory tachycardia during the early phase of one kidney, one clip (1K1C) hypertension in the rat, when the basal heart rate (HR) is measured daily under resting conditions. In the present study, in control rats, marked tachycardia (406 +/- 11 vs 320 +/- 4 bpm during the control period) was observed on the first day of electrolytic lesion of the anteroventral third ventricle (AV3V) region. The basal HR declined progressively thereafter and was normal 14 days after AV3V lesion. The peak of tachycardia (388 +/- 12 bpm) observed 7 days after clipping in sham-lesioned rats did not occur in 1K1C AV3V-lesioned rats (318 +/- 5 bpm). However, hypertension was only partially (65%) abolished in the lesioned animals (135 +/- 4 vs 160 +/- 3 mm Hg in the sham-lesioned 1K1C). Captopril administered per os (30 mg/kg/day) for up to 20 days produced no change in the basal HR of sham-operated rats but abolished the initial tachycardia in 1K1C rats during the development of hypertension. Captopril also delayed the onset of renal hypertension, with mean arterial pressure reaching hypertensive levels only 2 weeks after clipping. These data indicate that integrity of the AV3V region is necessary for the occurrence of tachycardia during the onset of 1K1C hypertension. Since captopril abolished the tachycardia, the activity of converting enzyme seems to be important for the appearance of this phenomenon.

Microinjection of S-nitrosocysteine into the nucleus tractus solitarii of conscious rats decreases arterial pressure but L-glutamate does not.

Unilateral microinjection of L-glutamate into the nucleus tractus solitarii of conscious rats increased arterial pressure and caused bradycardia while microinjection of S-nitrosocysteine into the same site of these animals caused hypotension and bradycardia. The responses to S-nitrosocysteine were blocked by prior microinjection of methylene blue into the nucleus tractus solitarii. The bradycardia and fall in arterial pressure induced by S-nitrosocysteine resemble more the cardiovascular changes in response to activation of baroreceptor afferents than the bradycardia and increase in arterial pressure induced by microinjection of L-glutamate into the nucleus tractus solitarii of conscious rats.