Aortic Baroreceptor Denervation Research Articles

Abstract P395: A New Technique for Selective Denervation of the Aortic and Carotid Baroreceptors

The traditional sinoaortic denervation (SAD) technique in rats includes aortic and carotid baroreceptors denervation, but also leads to concomitant denervation of the carotid chemoreceptors. Here we report a new technique to denervate the carotid and aortic baroreceptors, selectively, preserving the carotid chemoreceptors intact. Wistar rats were subjected to selective aortic and carotid baroreceptor denervation sparing the carotid chemoreceptors intact (BAROS-X), or sham surgery (SHAM). The animals were also implanted with femoral arterial and venous catheter for arterial pressure recording and drug administration. In unanesthetized, freely moving rats, baroreflex or peripheral chemoreflex activation was elicited by intravenous injection of phenylephrine or potassium cyanide (KCN), respectively. Phenylephrine caused a significant hypertensive response in SHAM (Δ = 46 ± 3 mmHg, P<0.001) and BAROS-X (Δ = 38 ± 3 mmHg, P<0.001) combined with a reflex bradycardia in SHAM (Δ = -54 ± 11 bpm, P<0.001) but no change in heart rate in BAROS-X subjects (Δ = -5 ± 2 bpm, ns); confirming the absence of aortic and carotid baroreceptors in BAROS-X rats. KCN elicited significant hypertensive response in SHAM (44 ± 6 mmHg, P<0.001) and BAROS-X (39 ± 5 mmHg, P<0.001) subjects followed by bradycardic response in SHAM (-88 ± 17 bpm, P<0.001) and BAROX-S (-103 ± 23 bpm, P<0.01) rats; confirming that the carotid chemoreceptors were intact in both groups. These data provide support to a new surgical technique that allows working with conscious rats exhibiting selective inactivation of the aortic and carotid baroreceptors, combined with intact carotid chemoreceptors.

Responses of neurons in paraventricular nucleus to activation of cardiac afferents and acute myocardial ischaemia in rats

Stimulation of cardiac sympathetic afferents increases sympathetic outflow and blood pressure. Chemicals released during myocardial ischaemia activate cardiac afferents. This study was to determine the responses of neurons in paraventricular nucleus (PVN) to the cardiac afferent activation caused by exogenous chemicals or myocardial ischaemia using an extracellular single-unit recording method. Rats were anaesthetized and underwent bilateral cervical vagal denervation (VD) and carotid and aortic baroreceptor denervation (BD). In 196 spontaneously active neurons in parvicellular PVN, 60 (30.6%), 36 (18.4%) and 91 (46.4%) neurons were respectively sensitive, mildly sensitive and insensitive to capsaicin, while nine (4.6%) neurons showed inhibitory responses to capsaicin. Epicardial application of capsaicin activated capsaicin-sensitive neurons in the PVN and increased mean arterial pressure. These neurons were also sensitive to exogenous bradykinin, adenosine and H(2)O(2). The neuron response is not secondary to a capsaicin-induced increase in mean arterial pressure because a similar degree of pressor response induced by aortic coarctation did not increase the neuron activity. Compared with intact rats, VD or BD or combined VD and BD increased the response of capsaicin-sensitive neurons to epicardial application of capsaicin, while stimulation of vagal afferents inhibited the response. Myocardial ischaemia caused increases in the activity of capsaicin-sensitive neurons and renal sympathetic nerve activity. The results indicate that chemical stimulation of cardiac sympathetic afferents activates capsaicin-sensitive neurons in parvicellular PVN, which is inhibited by the afferent activities of vagi and arterial baroreceptors. Acute myocardial ischaemia activates capsaicin-sensitive neurons in PVN and enhances sympathetic outflow.

Chronic Aortic Barodenervation switches salt‐sensitive normotension to salt‐sensitive hypertension in rats

Our prior (EB08 Abs.738.4) cross sectional study suggested that bilateral chronic aortic baroreceptor denervation (AD) induces salt‐sensitive normotension in rats. To assess this in depth, mean arterial pressure (MAP) was measured intra‐arterially over time (3 times) in two groups of conscious Wistar rats. The first time (PreDen) was measured in caudal artery before random sham (SH, n = 7) or real AD (n = 10); the second one was measured in left femoral artery after 7 days on low sodium diet (PostDen LNaD = 0.04% Na) and the third time was measured in right femoral artery after 21 days on high sodium diet (PostDen HNaD = 8% Na). The effectiveness of AD was judged by Box‐Cox transformation of PHE(1) and SNP (2) slope [((( [3 ‐ (HR2‐HR1/ MAP2‐MAP1)] −0.4) ‐1) / ‐0.046)] obtained in conscious state. Salt Sensitivity = SS = (PostDen HNaD MAP ‐ PostDen LNaD MAP, mmHg). Delta of MAP (PostDen MAP ‐ PreDen MAP, mmHg) on both LNaD and HNaD were calculated too. &p = 0.05, *p <0.003 vs SH and + p < 0.01, # p < 0.009 vs LNaD.PreDen PostDen PostDen SS Delta MAP DeltaMAPLNaD HNaD LNaD HNaDSH 105.0 114.0 122.0+ 7.7 9.0 16.7+±2.7 ±1.8 ±1.7 ±2.5 ±2.6 ±2.3AD 101.0 123.2& 134.5*# 11.3 22.2* 33.5*#±2.0 ±2.4 ±2.8 ±2.6 ±2.0 ±2.4ConclusionsWistar rats show salt‐sensitive normotension that chronic AD switches to salt‐sensitive hypertension. Supported by: CONACYT 62282

Lesions of the Commissural Nucleus of the Solitary Tract Reduce Arterial Pressure in Spontaneously Hypertensive Rats

It has been suggested that increased sympathetic activity and arterial chemoreceptors are important for the high blood pressure in spontaneously hypertensive rats (SHR). Electrolytic lesions of the commissural nucleus of the solitary tract (commNTS) abolish (1) the cardiovascular responses to chemoreflex activation with potassium cyanide (KCN) in normotensive rats and (2) the hypertension that follows acute aortic baroreceptor denervation in rats. Therefore, in this study we investigated the effects of electrolytic lesions of the commNTS on basal mean arterial pressure (MAP), baroreflex, and chemoreflex in SHR and in normotensive control Wistar-Kyoto (WKY) and Wistar rats. CommNTS lesions elicited a dramatic fall in MAP to normal levels during the period of study (from the first to fourth day following lesions) in SHR and almost no changes in WKY and Wistar rats. The pressor responses to chemoreflex activation with KCN tested in the days 1 and 4 after commNTS lesions were abolished in SHR and in normotensive strains. The reflex tachycardia induced by sodium nitroprusside was also attenuated in days 1 and 4 after commNTS lesions in SHR, WKY, and Wistar rats. The data suggest that the integrity of commNTS is important for the maintenance of high blood pressure in SHR and for the reflex responses dependent on sympathetic activation either in SHR or in normotensive strains.

Effect of carotid or aortic baroreceptor denervation on arterial pressure during hemorrhage in conscious dogs.

We studied the effect of chronically denervating aortic baroreceptors (ABR; n = 6) or carotid baroreceptors (CBR; n = 7) on mean arterial pressure (MAP) and heart rate (HR) responses to hemorrhage in the dog. Neither denervation had a significant effect on basal MAP, the variability (standard deviation) of MAP, or resting HR. However, the breakpoint of MAP (defined as the volume of blood removed when MAP fell more than 10% below control and declined monotonically thereafter) was significantly reduced in dogs with only ABR functional (12.4 +/- 1.4 ml/kg) compared with the volume in the intact condition (18.9 +/- 1.8 ml/kg). In contrast, there was no difference in the breakpoint or the MAP at any time during hemorrhage in dogs with both CBR functional compared with their intact responses. In a different group of dogs (n = 6), responses were determined with both CBR operating and again after unilateral denervation, leaving only one CBR (1CBR) functional. Basal MAP and the variability of MAP were not altered in dogs with only 1CBR functional, but the breakpoint (11.7 +/- 1.4 ml/kg) during hemorrhage was significantly different compared with responses with two CBR (21.2 +/- 2.3 ml/kg), and MAP fell to much lower levels. These results indicate that the CBR can compensate fully for loss of ABR during hemorrhage but not vice versa; and bilateral CBR inputs are required for normal responses to hemorrhage.

Commissural NTS lesions and cardiovascular responses in aortic baroreceptor-denervated rats.

Both acute (1 day) lesions of the commissural nucleus of the solitary tract (commNTS) and aortic baroreceptor denervation increase pressor responses to bilateral common carotid occlusion (BCO) during a 60-second period in conscious rats. In this study, we investigated the following: (1) the effects of commNTS lesions on basal mean arterial pressure (MAP) and heart rate (HR) of aortic denervated (ADNx) rats; (2) the effects of acute commNTS lesions on pressor responses to BCO in ADNx rats; and (3) the effects of chronic (10 days) commNTS lesions on the pressor response to BCO. ADNx increased basal MAP and HR in sham-lesioned rats. Acute commNTS lesions abolished the MAP and HR increases observed in ADNx rats. Acute commNTS lesions increased the pressor responses to BCO in rats with intact-baroreceptor innervation but produced no additional change in the pressor response to BCO in ADNx rats. Chronic commNTS lesions did not change the pressor responses to BCO in rats with intact-baroreceptor innervation. The data show that acute commNTS lesions abolish the MAP increase produced by aortic baroreceptor denervation. They also suggest that acute commNTS lesions enhance the pressor response to BCO by partial withdrawal of aortic baroreceptor inputs into the NTS. Chronically, reorganization in the remaining aortic baroreceptor or in the baroreflex function as a whole might produce normalization of the cardiovascular responses to BCO.

Role of glutamate receptors in transmission of vagal cardiac input to neurones in the nucleus tractus solitarii in dogs.

1. Vagal afferent input from cardiac mechanoreceptors excites neurones in the nucleus tractus solitarii (NTS), but discharge patterns evoked by physiological activation of pressure-sensitive cardiac mechanoreceptors have not been studied in vivo. The role of glutamate receptor subtypes in transmission of afferent activity to the NTS neurones has not been determined. The present study therefore has two aims: first, to characterise the discharge patterns of neurones in the NTS that receive pressure-sensitive vagal cardiac receptor input and second, to determine the roles of ionotropic glutamate receptor subtypes in the transmission of this putative cardiac mechanoreceptor-related activity to NTS neurones. 2. Pulse-synchronous activity of neurones in the NTS evoked by vagal afferent input was recorded extracellularly in an anaesthetised dog model using multibarrel glass electrodes, which allowed picoejection of the glutamate receptor antagonists NBQX or AP5 to block either non-NMDA or NMDA receptors, respectively, during the neuronal recording. Pressure sensitivity of the recorded neurones was examined by monitoring their response to a small increase in arterial blood pressure. Selective pressure activation of carotid sinus baroreceptors in an isolated sinus or selective denervation of aortic baroreceptors were used to test for convergent excitation of the neurones by arterial baroreceptors. 3. Pulse-synchronous cardiac-related neuronal activity recorded from neurones in both the right and left NTS was eliminated following section of the left (n = 17) or right (n = 1) vagus nerves. No spontaneous, non-pulsatile activity was observed in these neurones before or after vagotomy. Activity transmitted via left vagal afferents was found to be sensitive to changes in arterial blood pressure. In these neurones, activity was blocked in 13 of 17 neurones by picoejection of NBQX, with the remainder requiring both NBQX and AP5. None of the cardiac-related neurones responded to activation of carotid baroreceptors or denervation of aortic baroreceptors, indicating no convergence of activity from carotid baroreceptors or aortic baroreceptors with pressure thresholds of approximately 130 mmHg or less. 4. The results suggest that vagal pressure-sensitive afferent input from cardiac mechanoreceptors is transmitted primarily by left vagal afferent fibres via non-NMDA receptors to neurones in both the ipsilateral and contralateral NTS. NMDA receptors were also found to have a role in the activation of a small subpopulation of neurones.

Ethanol abolishes clonidine-induced impairment of baroreflex control of heart rate in conscious rats

Our previous studies showed that the ability of ethanol or cholidine to alter the baroreflex control of heart rate (baroreflex sensitivity, BRS) depends on the functional activity of aortic baroreflexes. In this study, we investigated the interaction between the two drugs on BRS in conscious rats with intact baroreflexes (shamoperated, SO) and after aortic baroreceptor denervation (ABD). The slope of the curve relating increments in mean arterial pressure induced by phenylephrine to corresponding reflex bradycardic responses was taken as an index of BRS. Ethanol (1 g/kg IV) significantly (p < 0.05) attenuated BRS in SO rats (−1.7 ± 0.13 versus −1.04 ± 0.15 beats/min/mm Hg) but not in ABD rats. Clonidine (30 μg/kg, IV) elicited significantly (p < 0.05) greater hypotensive responses in conscious ABD compared with SO rats. The BRS was not affected by clonidine administration in SO rats but showed significant (p < 0.05) reductions in ABD rats. Ethanol (1 g/kg, IV) had no effect on the hypotensive response to subsequently administered clonidine in ABD and SO rats; however, the effect of the two drugs on BRS was variable. In ABD rats, the BRS values before and after administration of ethanol and clondine were similar, suggesting that pretreatment with ethanol counteracted clonidine-evoked attenuation of BRS in this rat preparation. In SO rats, the ethanol–clonidine combination produced a significant (p < 0.05) decrease in BRS, similar to the effect of ethanol when administered alone. These data confirm earlier findings that the aortic baroreflex arc modulates the interaction of ethanol and clonidine with baroreflex function. Further, the ability of ethanol to abolish clonidine-induced attenuation of BRS in ABD rats may relate to the compound effects of the two drugs on neuronal pathways participating in the central processing of baroreflexes in these rats.

Short-term aortic barodenervation diminishes α 1-adrenoceptor reactivity in rat aortic smooth muscle

Our previous studies have shown that aortic baroreceptor denervation elicits acute increases in blood pressure and significant elevations of sympathetic activity and peripheral vascular resistance. This study investigated the short-term (3 and 48 h) effect of aortic barodenervation and associated sympathetic hyperactivity on the functional activity of α 1-adrenoceptors in rat aortic smooth muscle. Compared with sham operation, aortic barodenervation caused acute rises in blood pressure and heart rate and reductions in baroreflex sensitivity. Blood pressure and heart rate remained elevated when measured in conscious aortic barodenervated rats 3 h after surgery but subsided to sham-operated levels at 48 h; the baroreflex sensitivity, however, remained attenuated. Hexamethonium (0.5–4 mg/kg, i.v.) elicited significantly ( P<0.05) greater depressor responses in conscious aortic barodenervated rats than in sham-operated rats at both 3 and 48 h, suggesting a higher sympathetic activity in denervated rats. Exposure of aortic rings from aortic barodenervated and sham-operated rats to cumulative addition of phenylephrine (α 1-adrenoceptor agonist, 3×10 −8–1×10 −4 M) resulted in concentration-related contractile responses that were similar in the two groups of rats at 3 h in contrast to significantly ( P<0.05) smaller contractions in rings from denervated rats at 48 h. The maximum contraction developed ( E max) at 48 h showed approximately 50% reduction in rings from aortic barodenervated compared with sham-operated rats (239±16 vs. 558±15 mg tension/mg tissue). The pA 2 value for prazosin (α 1-adrenoceptor antagonist) was not altered by aortic barodenervation at 3 h but showed significant ( P<0.05) increases, compared with sham-operated values, at 48 h. It is concluded that short-term aortic barodenervation results in an elevation of sympathetic activity that coincides with reduced responsiveness of aortic smooth muscle to α 1-adrenoceptor activation. The aortic barodenervation-induced α 1-adrenoceptor desensitization is not a result of decreased receptor affinity but may involve an alteration of receptor density or in the post-receptor activation events. © 1997 Elsevier Science B.V. All rights reserved.

Influence of aortic baroreceptor denervation on adenosine receptor-mediated relaxation of isolated rat aorta

The effect of aortic baroreceptor denervation on the vasorelaxant activity of the adenosine analogue, 5′-N-ethylcarboxamidoadenosine (NECA) was evaluated in the isolated thoracic aortic rings from rats. The responses were evaluated at 3 h after baroreceptor denervation when the blood pressure was significantly higher than that of control (149±3 vs. 112±2 mmHg) and at 48 h after aortic baroreceptor denervation when blood pressure returned to control level. Sham operation had no effect on blood pressure at either time interval. A concentration-dependent relaxation of rat aorta elicited by NECA was observed in all groups. However, the responsiveness to NECA was reduced in aortic baroreceptor-denervated rats. The nitric oxide (NO) synthase inhibitor, L-monomethyl- L-arginine (30 μM) shifted the dose-response curve for NECA to the right in all groups suggesting that the vascular response to NECA is partially mediated through the release of NO. Removal of the endothelium abolished the differences in the response to NECA in sham and aortic baroreceptor-denervated rats suggesting that the decrease in the responsiveness of aortic smooth muscle to NECA is dependent on the release of NO. Vasorelaxant responses to acetylcholine were not altered by aortic baroreceptor denervation. The ability of aortic baroreceptor denervation to attenuate vasorelaxant responses to NECA but not to acetylcholine indicated the possibility of functional changes involving adenosine receptor-mediated relaxation in endothelium rather than structural changes due to aortic baroreceptor denervation. These findings suggest that short-term elevation of blood pressure following aortic baroreceptor denervation modulates the endothelium-dependent release of NO mediated by adenosine receptor activation.

Normalization of arterial pressure after barodenervation: role of pressure natriuresis

Studies in several species have demonstrated that mean arterial pressure (MAP) is normal or only slightly elevated after chronic arterial baroreceptor denervation. We hypothesized that the absence of sustained hypertension after barodenervation was the result of a pressure natriuresis response, secondary to sympathetic vasoconstriction of nonrenal vasculature. To test this hypothesis, MAP, sodium balance (NaBal), and water balance were measured before and after aortic baroreceptor denervation (ABD), sinoaortic denervation (SAD), or sham surgery in conscious rats. MAP was increased 20.0 +/- 3.7 mmHg 1 day after ABD but returned to control by day 3. ABD had no significant effect on daily NaBal or water balance. The responses to SAD were similar to those after ABD, with the exception that a significant natriuresis was observed the first day after SAD. However, this was followed by a significant antinatriuresis on day 2, when MAP was still elevated. By day 3 after SAD, MAP, NaBal, and water balance were not significantly different from control. These results suggest that the normalization of MAP after ABD or SAD is not the result of pressure natriuresis but rather failure to maintain a chronic elevation of sympathetic activity after barodenervation.

Cardiovascular purinoceptors

Cardiovascular purinoceptors

Acute carotid baroreflex resetting in conscious dogs.

1. Acute baroreflex resetting in the control of arterial pressure was studied in six chronically instrumented, conscious dogs. Following aortic baroreceptor denervation, the carotid sinuses were surgically prepared for reversible vascular isolation. 2. During the experiments both carotid sinuses were temporarily isolated from the systemic circulation and conditioned with a pulsatile pressure. The carotid sinus conditioning pressure (CPCSP) was at a level of 100, 140 or 60 mmHg for 20 min each. Carotid sinus pressure (CSP) versus mean arterial pressure (MAP) baroreflex curves were constructed after each conditioning period. 3. The baroreflex curves were shifted downward and to the left at low CPCSP and upward and to the right at high CPCSP. 4. We used four parameters to quantify baroreflex resetting. These were: (1) the set point pressure (PSP), (2) the threshold pressure (PTh), (3) BP50 or mid-point pressure and (4) the CSP at maximum gain (PGmax). At high CPCSP, these four parameters were increased by 18.5 +/- 4.0, 23.4 +/- 4.3, 21.7 +/- 5.0 and 22.0 +/- 5.1 mmHg, respectively (P less than 0.05). 5. Resetting was not complete in these studies. The extent of resetting was approximately 50% for upward and 35% for downward baroreflex conditioning. 6. Analysis of the present experimental data indicates that when the cardiovascular system is exposed to a short-term hyper- or hypotension, the baroreflex is capable of correcting the baseline arterial pressure while preserving its ability to buffer transient disturbances as a result of partial resetting.

The influence of cardiopulmonary receptors on long-term blood pressure control and plasma renin activity in conscious dogs.

The isolated and combined influence of cardiopulmonary and arterial baroreceptor denervation on long-term blood pressure (MAP), heart rate (HR), plasma volume (PV) and plasma renin activity (PRA) was studied in 10 conscious, chronically instrumented foxhounds receiving a normal sodium diet. Cardiopulmonary denervation was achieved by surgically stripping both thoracic vagi. Near complete arterial baroreceptor denervation, leaving most cardiopulmonary fibres intact, was made by left vagal deafferentiation which has been shown to eliminate most aortic baroreceptor afferents, and a carotid sinus denervation. Five groups were studied: (I) control (n = 9), (II) cardiopulmonary denervation (n = 5), (III) aortic baroreceptor denervation (n = 5), (IV) arterial baroreceptor denervation (n = 4) and (V) total denervation (n = 6). No changes in PV were observed. Only group V revealed significantly higher levels of MAP (119.5 +/- 5.4 vs. 100.1 +/- 1.6 mmHg; P less than 0.05), HR (118.1 +/- 4.4 vs. 87.8 +/- 3.7 beats min-1; P less than 0.001) and PRA (3.0 +/- 0.8 vs. 0.9 +/- 0.2 ng AI m-1 h-1; P less than 0.05). It is suggested that the isolated function of either cardiopulmonary or arterial baroreceptors is sufficient to maintain these variables at a normal level. Contrary to the results of other reports the cardiopulmonary receptors do not seem to regulate MAP at a level about which the arterial baroreceptors operate. When both groups of afferents were interrupted MAP, HR and PRA rose to significantly higher levels, implying that cardiopulmonary and arterial baroreceptor afferents interact in a sense of a non-additive attenuation.

Changes in forebrain hexokinase activity after aortic baroreceptor denervation.

Although forebrain structures have been implicated in both the development and maintenance of the elevated arterial pressure (AP) after aortic baroreceptor denervation, little is known about the location of central structures involved in the hypertensive process. In the present study, regions of the forebrain whose metabolic activity was altered after aortic baroreceptor denervation were functionally identified using hexokinase (HK) histochemistry in the rat. Three days after bilateral aortic depressor nerve (ADN) transection AP was significantly elevated compared with sham ADN-transected animals (143 +/- 1 and 122 +/- 2 mmHg, respectively). Significant increases in HK activity were observed in the magno- and parvocellular components of the paraventricular nucleus of the hypothalamus, supraoptic nucleus, nucleus circularis, median preoptic nucleus, subfornical organ, and central nucleus of the amygdala in the ADN-transected animals. These data have demonstrated that removal of aortic baroreceptor afferent inputs alters the activity of forebrain structures previously implicated in regulation of body fluid balance and AP and suggest that these structures are involved in the hypertensive process after ADN transection.

Kainic acid lesions of paraventricular nucleus neurons reverse the elevated arterial pressure after aortic baroreceptor denervation in the rat

The effect of selective destruction of neurons of the paraventricular nucleus of the hypothalamus (PVH) with kainic acid on the maintenance of the elevated arterial pressure (AP) and heart rate (HR) after aortic baroreceptor denervation was investigated in male Wistar rats. The average AP and HR were significantly elevated in two groups of animals which were subjected to bilateral aortic depressor nerve (ADN) transection compared to sham-ADN-transected animals. Microinjections of kainic acid bilaterally into the PVH reduced the elevated AP and HR in ADN-transected animals to levels which were not significantly different from either sham-ADN-transected animals which received kainic acid injections into the PVH or from predenervation levels. AP and HR in the sham-ADN-transected animals which received bilateral PVH injections of kanic acid were not altered from prelesioned levels. As magnocellular neurons of the PVH have been shown to be resistant to the neurotoxic effects of kainic acid, these data indicate that PVH parvocellular neurons are required for the maintenance of the elevated AP and HR resulting from the removal of aortic baroreceptor inputs to the central nervous system.

Effect of paraventricular nucleus lesions on arterial pressure and heart rate after aortic baroreceptor denervation in the rat

Two series of experiments were done in male Wistar rats to investigate the effects of lesions of the paraventricular nucleus of the hypothalamus (PVH) on the maintenance and development of the elevated arterial pressure resulting from denervation of aortic baroreceptors. In the first series, after control recordings of arterial pressure (AP) and heart rate (HR), rats were subjected to either bilateral aortic depressor nerve (ADN) transection or sham-ADN. These animals were later subjected to either bilateral lesions of the PVH or sham-PVH lesions. AP ( 146 ± 2mm Hg) and HR ( 515 ± 5bpm) were significantly elevated in only the ADN-transected groups. Bilateral lesions of the PVH significantly reduced AP ( 119 ± 3mm Hg) and HR ( 440 ± 8bpm) in the ADN transected animals compared to ADN-transected sham-PVH-lesioned animals, to levels which were not significantly different from pre-ADN-transected levels ( AP113 ± 2mm Hg; HR, 448 ± 3bpm, and from sham-ADN-transected PVH-lesioned ( AP, 119 ± 2mm Hg; HR, 391 ± 6bpm and sham-ADN-transected sham-PVH-lesioned animals ( AP, 116 ± 2mHg; HR, 436 ± 4bpm). In the second series of experiments after control AP and HR recordings rats were first subjected to either bilateral lesions of the PVH or sham-PVH lesions, and second to either bilateral ADN transection or sham-ADN transection. PVH lesions did not significantly alter the AP and HR from control levels. However, AP and HR in the ADN-transected rats were significantly higher in the sham-PVH-lesioned rats compared to the PVH-lesioned ADN-transected, PVH-lesioned sham-ADN-transected and sham-PVH-lesioned sham-ADN-transected animals. These data demonstrate that the PVH plays an important role in both the maintenance and development of the increased AP and HR resulting from aortic baroreceptor deafferentation and that these cardiovascular changes are dependent on the integrity of this structure.

Occlusive summation of carotid and aortic baroreflexes in control of renal nerve activity.

We recently reported that denervation of aortic or carotid baroreceptors impaired baroreflex control of heart rate but not of hindlimb vascular resistance or lumbar sympathetic nerve activity. Since baroreflex control of sympathetic outflow to different vascular beds is nonuniform, we determined whether carotid or aortic baroreceptor denervation would impair baroreflex control of renal nerve activity. Experiments were performed in 23 alpha-chloralose-anesthetized rabbits. Phenylephrine and nitroglycerin were infused to raise or lower arterial pressure. Pressure elevation inhibited and pressure reduction increased renal nerve activity. The linear regression relationships between changes in arterial pressure and percent change in renal nerve activity were determined with baroreflexes intact and after aortic or carotid denervation. Neither carotid nor aortic denervation alone impaired baroreflex control of renal nerve activity. In nine experiments responses were determined first with vagi sectioned. The results were comparable to those obtained without prior vagotomy. Our data indicate that one group of baroreceptors (aortic or carotid) exerts full control of renal nerve activity and that aortic and carotid baroreflex influences on renal nerve activity add by occlusive or mutual inhibitory summation.

Participation of adrenergic and noradrenergic neurones in central connections of arterial baroreceptor reflexes in the rat.

We examined activities of tyrosine hydroxylase (TH) and phenylethanolamine-N-methyl transferase (PNMT) and concentrations of norepinephrine (NE) in seven brain regions and the spinal cord of Wistar rats with elevated blood pressures 1 week and 4 weeks after denervation of carotid and aortic baroreceptors, and compared them to values in sham-operated control rats. TH activity was increased in the solitary tract nucleus (to 188% of control), parahypoglossal nucleus (to 254%), locus ceruleus (to 191%), and posterior hypothalamus (to 225%) at 1 week but not at 4 weeks after denervation. Similarly, NE concentrations were significantly altered in a number of brain regions at 1 week but not at 4 weeks after denervation. The only change in NE concentration at 4 weeks was in spinal cord where the level was reduced to 80% of control in the denervated rats. In contrast, the only change in PNMT activity 1 week after denervation was in posterior hypothalamus (to 59% of control), whereas at 4 weeks there was in increase in the spinal cord (to 159%) and a decrease in both the anterior and posterior hypothalamus (to 59% and 64% of control, respectively). The experiments suggest that increased activity of noradrenergic neurones in the brain may play a significant role in initiating the increase in pressure produced by baroreceptor denervation, whereas decreased activity of hypothalamic adrenergic neurones may be more important in maintaining the raised pressure. An increase in the activity of both adrenergic and noradrenergic nerves in the spinal cord, however, could contribute to maintaining the increase in blood pressure 4 weeks after denervation.

Hypertension following denervation of aortic baroreceptors in unanesthetized dogs.

After cervical aortic nerve section, mean arterial pressure in the unanesthetized dog increased by an average of 7.4 mm Hg. Following a more extensive denervation of aortic arch receptors by section of intrathoracic vagal branches, arterial pressure increased by 16.7 mm Hg. The above changes were seen in the stable state after the effects of surgery had disappeared. In both cases carotid baroreceptors were functional. After administration of nitroglycerin and phenylephrine subsequent to either denervation procedure, blood pressure changes were larger and heart rate responses were smaller than in the control state. The unanesthetized dog regulates mean arterial pressure at a higher-than-normal pressure after aortic baroreceptor denervation. Reflexes from the aortic baroreceptors continuously participate in the normal control of mean arterial pressure. Section of the cervical aortic nerves only partially denervates aortic baroreceptors. Our findings may be relevant to human essential hypertension.