Sinoaortic Denervation Research Articles

An improved strategy for evaluating the extent of chronic arterial baroreceptor denervation in conscious rats

There is no index or criterion of aortic barodenervation, nor can we differentiate among rats that have suffered chronic sham, aortic or sino-aortic denervation. The objective of this study was to develop a procedure to generate at least one quantitative, reproducible and validated index that precisely evaluates the extent of chronic arterial barodenervation performed in conscious rats. Data from 79 conscious male Wistar rats of about 65-70 days of age with diverse extents of chronic arterial barodenervation and used in previous experiments were reanalyzed. The mean arterial pressure (MAP) and the heart rate (HR) of all rats were measured systematically before (over 1 h) and after three consecutive iv bolus injections of phenylephrine (PHE) and sodium nitroprusside (SNP). Four expressions of the effectiveness of barodenervation (MAP lability, PHE ratio, SNP ratio, and SNP-PHE slope) were assessed with linear fixed models, three-level average variance, average separation among levels, outlier box plot analysis, and overlapping graphic analysis. The analysis indicated that a) neither MAP lability nor SNP-PHE slope was affected by the level of chronic sodium intake; b) even though the Box-Cox transformations of both MAP lability [transformed lability index (TLI)] and SNP-PHE slope [transformed general sensitivity index (TGSI), {((3-(ΔHR(SNP)-ΔHR(PHE)/ΔMAP(SNP)-ΔMAP(PHE)))(-0.4)-1)/-0.04597}] could be two promising indexes, TGSI proved to be the best index; c) TLI and TGSI were not freely interchangeable indexes for this purpose. TGSI ranges that permit differentiation between sham (10.09 to 11.46), aortic (8.40 to 9.94) and sino-aortic (7.68 to 8.24) barodenervated conscious rats were defined.

Sinoaortic Denervation Prevents Enhanced Heat Loss Induced By Central Cholinergic Stimulation During Physical Exercise.

Sinoaortic Denervation Prevents Enhanced Heat Loss Induced By Central Cholinergic Stimulation During Physical Exercise.

Differential control of renal and lumbar sympathetic nerve activity during freezing behavior in conscious rats

The present study was designed to document changes in sympathetic nerve activity and cardiovascular function when conscious rats were challenged with a noise stressor to induce freezing behavior. The potential contribution of the arterial baroreceptors in regulating sympathetic nerve activity and cardiovascular adjustments during the freezing behavior was then examined. Wistar male rats were assigned to sham-operated (SO) and sinoaortic-denervated (SAD) groups and instrumented chronically with electrodes for measurements of renal (RSNA) and lumbar (LSNA) sympathetic nerve activity, electroencephalogram, electromyogram, and electrocardiogram and catheters for measurements of systemic arterial and central venous pressure. Both SO and SAD rats were exposed to 90 dB of white noise for 10 min, causing freezing behavior in both groups. In SO rats, freezing behavior was associated with an immediate and significant (P < 0.05) increase in RSNA, no changes in LSNA or mean arterial pressure, and a significant (P < 0.05) decrease in heart rate. SAD attenuated the magnitude of the immediate increase in RSNA and had no influence on the response in LSNA during freezing behavior compared with SO rats. Moreover, in SAD rats, mean arterial pressure increased significantly (P < 0.05) while heart rate did not change during the freezing behavior. These data indicate that freezing behavior evokes regionally different changes in sympathetic outflows, which may be involved in generating the patterned responses of cardiovascular function to stressful or threatening sensory stimulation. Moreover, it is suggested that the arterial baroreceptors are involved in generating the differential changes in RSNA and LSNA and thus the patterned changes in cardiovascular functions observed during freezing behavior in conscious rats.

Sustained suppression of sympathetic activity and arterial pressure during chronic activation of the carotid baroreflex

Following sinoaortic denervation, which eliminates arterial baroreceptor input into the brain, there are slowly developing adaptations that abolish initial sympathetic activation and hypertension. In comparison, electrical stimulation of the carotid sinus for 1 wk produces sustained reductions in sympathetic activity and arterial pressure. However, whether compensations occur subsequently to diminish these responses is unclear. Therefore, we determined whether there are important central and/or peripheral adaptations that diminish the sympathoinhibitory and blood pressure-lowering effects of more sustained carotid sinus stimulation. To this end, we measured whole body plasma norepinephrine spillover and alpha(1)-adrenergic vascular reactivity in six dogs over a 3-wk period of baroreflex activation. During the first week of baroreflex activation, there was an approximately 45% decrease in plasma norepinephrine spillover, along with reductions in mean arterial pressure and heart rate of approximately 20 mmHg and 15 beats/min, respectively; additionally, plasma renin activity did not increase. Most importantly, these responses during week 1 were largely sustained throughout the 3 wk of baroreflex activation. Acute pressor responses to alpha-adrenergic stimulation during ganglionic blockade were similar throughout the study, indicating no compensatory increases in adrenergic vascular reactivity. These findings indicate that the sympathoinhibition and lowering of blood pressure and heart rate induced by chronic activation of the carotid baroreflex are not diminished by adaptations in the brain and peripheral circulation. Furthermore, by providing evidence that baroreflexes have long-term effects on sympathetic activity and arterial pressure, they present a perspective that is opposite from studies of sinoaortic denervation.

The aortic and carotid sinus baroreflexes contribute equally to control blood pressure and heart rate variabilities

Baroreflexes are important in stabilizing blood pressure (BP). Disrupting the reflexes, e.g., via sinoaortic denervation (SAD), largely increases BP variability (BPV), which contributes to end‐organ damage. Because baroreflexes are often destructed separately in clinic, this study examines the individual role of aortic and carotid baroreflexes in BPV.Seven neuromuscular blocked (NMB), Sprague‐Dawley, female (225–275 g) rats were studied. Aortic denervation (AD, 4 rats) and carotid denervation (CD, 3 rats) were made sequentially, with initial denervation chosen in random order. BP and heart rate (HR) were recorded continuously for 10 hrs during baseline and denervation stages. BPV was defined by standard deviation (SD), and very low frequency (0.01–0.2 Hz) power of the BPV spectrum. Results: 1) Independent of denervation order, complete SAD greatly increased BPV: Compared to the baseline, SDs and VLF powers increased ~250% (AD→SAD: t=7.15, p&lt;.01; CD→SAD: t=12.75, p&lt;.01) and 130% (AD→SAD: t=10.59, p&lt;.01; CD→SAD: t=9.78, p=.01), respectively; 2) AD and CD each increased BPV: SDs increased ~100% and VLF powers ~80%; the increase was significant for AD (SD: t=8.88, p&lt;.0; and VLF: t=4.16, p&lt;.05), but not for CD. There was no difference between post‐ AD and CD BPV; and 3) Denervations had no effect on HR variability. Conclusion: Aortic and carotid baroreflexes contribute equally to BP and HR variabilities.

Sympathetic overactivity in sinoaortic denervated C57BL mice

Male C57BL mice were submitted to sinoaortic denervation (SAD), or sham surgery, implanted with catheters into femoral artery and jugular vein and let recover for 5 days. After basal recording of arterial pressure (AP) and pulse interval (PI) mice received cardiac autonomic receptor blockers methylatropine or propranolol (n=8–11 in each group). PI changes due to methylatropine or propranolol were measured as cardiac vagal and sympathetic tone, respectively. AP variability was calculated by standard deviation of successive values (SDNN) of systolic AP and PI variability determined by SDNN as well as by the square root of the mean squared differences of successive values of PI (RMSSD). Mean AP and SDNN of SAP was higher in SAD (149±3 and 10.0±0.5 mmHg) as compared to intact mice (136±2 and 6.5±0.4 mmHg). PI was similar between groups (104±3 vs 104±2 ms) while SDNN and RMSSD of PI were lower in SAD (5.4±0.7 and 2.0±0.2 ms) as compared to intact mice (8.2±0.8 and 2.7±0.3 ms). Atropine did not change PI of SAD (100±4 to 98±4 ms), while slightly decreased PI of control mice (103±2 to 96±2 ms, p&lt;0.05). The increase in PI elicited by propranolol was marked higher in SAD (98±6 to 144±9 ms) than in intact mice (98±4 to 124±3 ms). Five days after SAD mice showed mild hypertension with marked increase in AP variability and cardiac sympathetic tone.Support: FAPESP, CNPq and CAPES.

Sinoaortic Denervation (SAD) Prevents Training‐Induced Plasticity in Preautonomic Oxytocinergic and Vasopressinergic Pathways

Baroreceptor signaling plays a crucial role in driving training‐induced beneficial adjustments mediated by central autonomic pathways (Exp Physiol 2009;94:630–640; 947–960). We sought now to identify these pathways in WKY and SHR. Rats submitted to SAD or SHAM surgery were trained (55% VO2 max, for 3 month) or kept sedentary (S). After hemodynamic measurements at rest, rats were anesthetized for transcardiac perfusion (PBS). Brains were removed, frozen and sliced to isolate dorsal and ventral brain stem (comprising the solitary‐vagal complex and RVLM) and hypothalamic paraventricular nucleus (PVN); tissue samples were processed for oxytocin (OT), vasopressin (VP) and their receptors’ expression (Real Time PCR, GAPDH as the reporter gene). T‐induced pressure fall (−8% in the SHR) and resting bradycardia (−9% in both groups) were absent after SAD. There were no changes on receptors’ expression in target areas but SAD completely blocked T‐induced OT mRNA (4.3‐fold and 20% increases in SHAM WKYT and SHRT, respectively) and VP mRNA expression (+2.4‐fold in SHAM SHRT vs. S controls) within the PVN. OT and VP immunoreactivities within the PVN confirmed these responses. Baroreceptor inputs are decisive to drive plastic changes in preautonomic neurons. T‐induced PVN OTergic expression is present in both normotensive and hypertensive, while T‐induced VPergic expression is only observed in hypertensive individuals

Ionotropic glutamate receptors in the paraventricular nucleus (PVN) are required for sympathoexcitation due to angiotensin II (A II) in the subfornical organ (SFO) of nonpregnant and pregnant rats

Circulating A II is increased and CNS actions of A II may support sympathetic nerve activity (SNA) in pregnancy. We previously reported greater increases in mean arterial pressure (MAP) and lumbar SNA (LSNA) in response to AT1 receptor activation in the SFO in term pregnant (P) compared to nonpregnant (NP) rats. The pathway from the SFO requires AT1 receptors in the PVN. Ionotropic glutamate receptors (iGluRs) in the PVN also contribute to sympathoexcitation from the SFO and current experiments evaluated the role of iGluRs in the PVN. Responses to microinjection of A II into the SFO were tested before and after iGluR blockade (kynurenate, KYN) in the PVN. To eliminate compensatory arterial baroreflex responses, sinoaortic denervation was performed in 5 nonpregnant (NP) and 4 term pregnant (P) inactin anesthetized rats. Baseline MAP was lower in P (84±13 mmHg) compared to NP (124±11 mmHg) rats. Increases in MAP (ΔMAP: P = +16.5±3 mmHg; NP = +10±1 mmHg) and LSNA (ΔLSNA: P= 15±3%; NP= 8±1%) in response to A II (20 μM, 50 nl) in the SFO were greater in P rats. Bilateral microinjection of KYN (27 mM, 100 nl) into the PVN had minimal effects alone, but eliminated responses to activation of the SFO in both groups (ΔMAP: P= −1±1 mmHg; NP= −1±2 mmHg; ΔLSNA: P= 0±1%; NP= 1.5±1%) Thus, both iGluRs and AT1 receptors in the PVN are required for sympathoexcitation mediated by SFO A II in NP and P rats. (NIH HL 091164)

Angiotensin-(1–7) and angiotension II in the rostral ventrolateral medulla modulate the cardiac sympathetic afferent reflex and sympathetic activity in rats

The rostral ventrolateral medulla (RVLM) plays a pivotal role in regulating sympathetic vasomotor activity. The cardiac sympathetic afferent reflex (CSAR) contributes to the enhanced sympathetic outflow in chronic heart failure and hypertension. The aim of the present study was to determine whether angiotensin (Ang) II and Ang-(1-7) in the RVLM modulate the CSAR and sympathetic activity. Bilateral sinoaortic denervation and vagotomy were carried out in anesthetized rats. The CSAR was evaluated as the renal sympathetic nerve activity (RSNA) response to epicardial application of capsaicin. The effects of bilateral microinjection of Ang II, Ang-(1-7), the AT(1) receptor antagonist losartan or the Mas receptor antagonist D: -alanine-Ang-(1-7) (A-779) into the RVLM were determined. Either Ang II or Ang-(1-7) enhanced the CSAR as well as increased RSNA and mean arterial pressure (MAP) in a dose-dependent manner. Pretreatment with losartan but not the A-779 abolished the effects of Ang II, while A-779 but not the losartan eliminated the effects of Ang-(1-7). The RVLM microinjection of losartan alone had no direct effect on the CSAR, RSNA, and MAP, but A-779 alone attenuated the CSAR and decreased RSNA and MAP. These results indicate that Ang-(1-7) is as effective as Ang II in sensitizing the CSAR and increasing sympathetic outflow. In contrast to Ang II, the effects of Ang-(1-7) are not mediated by AT(1) receptors but by Mas receptors. Mas receptors, but not the AT(1) receptors, in the RVLM are involved in the tonic control of the CSAR.

Renin angiotensin system and cardiac hypertrophy after sinoaortic denervation in rats

OBJECTIVE:The aim of this study was to evaluate the role of angiotensin I, II and 1–7 on left ventricular hypertrophy of Wistar and spontaneously hypertensive rats submitted to sinoaortic denervation.METHODS:Ten weeks after sinoaortic denervation, hemodynamic and morphofunctional parameters were analyzed, and the left ventricle was dissected for biochemical analyses.RESULTS:Hypertensive groups (controls and denervated) showed an increase on mean blood pressure compared with normotensive ones (controls and denervated). Blood pressure variability was higher in denervated groups than in their respective controls. Left ventricular mass and collagen content were increased in the normotensive denervated and in both spontaneously hypertensive groups compared with Wistar controls. Both hypertensive groups presented a higher concentration of angiotensin II than Wistar controls, whereas angiotensin 1–7 concentration was decreased in the hypertensive denervated group in relation to the Wistar groups. There was no difference in angiotensin I concentration among groups.CONCLUSION:Our results suggest that not only blood pressure variability and reduced baroreflex sensitivity but also elevated levels of angiotensin II and a reduced concentration of angiotensin 1–7 may contribute to the development of left ventricular hypertrophy. These data indicate that baroreflex dysfunction associated with changes in the renin angiotensin system may be predictive factors of left ventricular hypertrophy and cardiac failure.

Long-term responses of renal sympathetic nerve activity and arterial pressure to chronic sino-aortic denervation in rats

Long-term responses of renal sympathetic nerve activity and arterial pressure to chronic sino-aortic denervation in rats

Evidence that blood pressure remains under the control of arterial baroreceptors in renal hypertensive rats

The purpose of the present study was to determine the range of the influence of the baroreflex on blood pressure in chronic renal hypertensive rats. Supramaximal electrical stimulation of the aortic depressor nerve and section of the baroreceptor nerves (sinoaortic denervation) were used to obtain a global analysis of the baroreceptor-sympathetic reflex in normotensive control and in chronic (2 months) 1-kidney, 1-clip hypertensive rats. The fall in blood pressure produced by electrical baroreceptor stimulation was greater in renal hypertensive rats than in normotensive controls (right nerve: -47 +/- 8 vs -23 +/- 4 mmHg; left nerve: -51 +/- 7 vs -30 +/- 4 mmHg; and both right and left nerves: -50 +/- 8 vs -30 +/- 4 mmHg; P < 0.05). Furthermore, the increase in blood pressure level produced by baroreceptor denervation in chronic renal hypertensive rats was similar to that observed in control animals 2-5 h (control: 163 +/- 5 vs 121 +/- 1 mmHg; 1K-1C: 203 +/- 7 vs 170 +/- 5 mmHg; P < 0.05) and 24 h (control: 149 +/- 3 vs 121 +/- 1 mmHg; 1K-1C: 198 +/- 8 vs 170 +/- 5 mmHg; P < 0.05) after sinoaortic denervation. Taken together, these data indicate that the central and peripheral components of the baroreflex are acting efficiently at higher arterial pressure in renal hypertensive rats when the aortic nerve is maximally stimulated or the activity is abolished.

Cardiovascular responses to intravenous injection of a novel isoindolin-1-one derivate in conscious rats

An isoindolin-1-one derivate, JM-1232(−), was recently developed as a sedative and hypnotic agent with a strong affinity for the central benzodiazepine binding site of gamma-aminobutyric acid A (GABA A) receptors. The purpose of this study was to examine the effects of JM-1232(−) on the cardiovascular and sympathetic functions of conscious rats. We investigated the effect of JM-1232(−) on the mean arterial pressure (MAP), heart rate (HR), baroreflex activity, and plasma catecholamine levels in conscious rats. The intravenous (i.v.) administration of JM-1232(−) (0.1, 0.3, and 1.0 mg/kg/min) for 20 min decreased MAP and increased HR in intact rats. In sinoaortic denervated (SAD) rats, JM-1232(−) decreased MAP and HR. A decrease in MAP induced by JM-1232(−) was prevented by pre-treatment with hexamethonium and enhanced by SAD. An increase in HR induced by JM-1232(−) was prevented by pre-treatment with atropine, propranolol, or hexamethonium. A decrease in MAP and an increase in HR induced by JM-1232(−) were antagonized by co-administration of flumazenil. A high dose of JM-1232(−) decreased the plasma norepinephrine concentration, and a subdepressor dose of JM-1232(−) did not affect the baroreceptor reflex. These results show that the i.v. administration of JM-1232(−) decreased MAP mediated by benzodiazepine–GABA A receptors.

Exaggerated Blood Pressure Variability Superimposed on Hypertension Aggravates Cardiac Remodeling in Rats via Angiotensin II System-Mediated Chronic Inflammation

Hypertensive patients with large blood pressure variability (BPV) have aggravated end-organ damage. However, the pathogenesis remains unknown. We investigated whether exaggerated BPV aggravates hypertensive cardiac remodeling and function by activating inflammation and angiotensin II-mediated mechanisms. A model of exaggerated BPV superimposed on chronic hypertension was created by performing bilateral sinoaortic denervation (SAD) in spontaneously hypertensive rats (SHRs). SAD increased BPV to a similar extent in Wistar Kyoto rats and SHRs without significant changes in mean blood pressure. SAD aggravated left ventricular and myocyte hypertrophy and myocardial fibrosis to a greater extent and impaired left ventricular systolic function in SHRs. SAD induced monocyte chemoattractant protein-1, transforming growth factor-beta, and angiotensinogen mRNA upregulations and macrophage infiltration of the heart in SHRs. The effects of SAD on cardiac remodeling and inflammation were much smaller in Wistar Kyoto rats compared with SHRs. Circulating levels of norepinephrine, the active form of renin, and inflammatory cytokines were not affected by SAD in Wistar Kyoto rats and SHRs. A subdepressor dose of candesartan abolished the SAD-induced left ventricular/myocyte hypertrophy, myocardial fibrosis, macrophage infiltration, and inductions of monocyte chemoattractant protein-1, transforming growth factor-beta, and angiotensinogen and subsequently prevented systolic dysfunction in SHRs with SAD. These findings suggest that exaggerated BPV induces chronic myocardial inflammation and thereby aggravates cardiac remodeling and systolic function in hypertensive hearts. The cardiac angiotensin II system may play a role in the pathogenesis of cardiac remodeling and dysfunction induced by a combination of hypertension and exaggerated BPV.

Chronic absence of baroreceptor inputs prevents training‐induced cardiovascular adjustments in normotensive and spontaneously hypertensive rats

We investigate whether arterial baroreceptors mediate the training-induced blood pressure fall and resting bradycardia in hypertensive (SHR) and normotensive rats (WKY). Male SHR and WKY rats, submitted to sino-aortic denervation (SAD) or sham surgery (SHAM group), were allocated to training (T; 55% of maximal exercise capacity) or sedentary (S) protocols for 3 months. Rats were instrumented with arterial and venous catheters for haemodynamic measurements at rest (power spectral analysis) and baroreceptor testing. Kidney and skeletal muscles were processed for morphometric analysis of arterioles. Elevated mean arterial pressure (MAP) and heart rate (HR) in SHAM SHRS were accompanied by increased sympathetic variability and arteriolar wall/lumen ratio [+3.4-fold on low-frequency (LF) power and +70%, respectively, versus WKYS, P < 0.05]. Training caused significant HR (approximately 9% in WKY and SHR) and MAP reductions (-8% in the SHR), simultaneously with improvement of baroreceptor reflex control of HR (SHR and WKY), LF reduction (with a positive correlation between LF power and MAP levels in the SHR) and normalization of wall/lumen ratio of the skeletal muscle arterioles (SHR only). In contrast, SAD increased pressure variability in both strains of rats, causing reductions in MAP (-13%) and arteriolar wall/lumen ratio (-35%) only in the SHRS. Training effects were completely blocked by SAD in both strains; in addition, after SAD the resting MAP and HR and the wall/lumen ratio of skeletal muscle arterioles were higher in SHRT versus SHRS and similar to those of SHAM SHRS. The lack of training-induced effects in the chronic absence of baroreceptor inputs strongly suggests that baroreceptor signalling plays a decisive role in driving beneficial training-induced cardiovascular adjustments.

Sinoaortic denervation prevents training‐induced plasticity in the central oxytocinergic (OT) system

Aerobic training (T) increase both ascending noradrenergic innervation to OT preautonomic neurons (Am J Physiol 2007;292:R1717) and OTmRNA expression within the hypothalamic paraventricular nucleus (PVN) (Hypertension 2005;46:1004), thus facilitating the slow down of the heart. We sought now to identify whether baroreceptor inputs affects T‐induced plasticity. WKY and SHR submitted to sinoaortic denervation (SAD) or SHAM surgery were trained (55% VO2 max, 5‐times/week, 1h/day) or kept sedentary (S) for 3 month. After pressure and heart rate (HR) measurement at rest, rats were anesthetized and perfused transcardiacally (0.01M PBS). Brains were removed, frozen and sliced to isolate dorsal brainstem (DBS, comprising the solitary‐vagal complex) and hypothalamic (directed to PVN) areas; tissue samples were processed for Real Time PCR. GAPDH was used as reporter gene. T‐induced pressure fall (‐8% in the SHR) and resting bradycardia (‐9% in both groups) were absent after SAD. SAD also completely blocked T‐induced OT mRNA expression in the PVN (4.3‐fold and 20% increases in SHAM WKYT and SHRT, respectively). Hypertension and SAD did not affect OT receptor expression within the DBS. In the chronic absence of baroreceptor inputs, the lack of plasticity on PVN OTergic neurons and HR response indicate that baroreceptor signaling plays a decisive role to drive beneficial T‐induced adjustments.SupportFAPESP, CNPq.

Sinoaortic denervation differentially reverses iliac, renal and mesenteric vasoconstriction evoked by stimulation of A1 adenosine receptors in the Nucleus of the Solitary Tract (NTS)

Activation of NTS A1 adenosine receptors evokes transient vasodilation followed by differential neural and vasopressinergic vasoconstriction in the iliac, mesenteric and renal vascular beds (FASEB, 21: A466, 2007). These responses may be partially mediated via inhibition of NTS baroreflex mechanisms (Am J Physiol 294: H172‐82, 2008). Therefore, in the present study we assessed the contribution of baroreflex mechanism to the regional vascular responses evoked by stimulation of NTS A1 adenosine receptors (CPA 330pmol/50nl) in urethane/chloralose anesthetized male Sprague Dawley rats. We compared the responses in iliac, mesenteric and renal vascular conductance evoked in intact vs. sinoaortic denervated (SAD) animals. SAD abolished vasoconstriction and accentuated vasodilation (iliac=mesenteric&gt;renal). Inasmuch as NTS A1 adenosine receptor mediated activation of the adrenal medulla partially persisted after SAD plus vagotomy or blockade of glutamatergic transmission in the NTS (Am J Physiol 283: H1588‐99, 2002) we conclude that the differential regional vasodilation observed in SAD animals is mediated mostly via non‐baroreflex activation of the adrenal medulla.

Activation of NTS A1 adenosine receptors impairs cardiopulmonary chemoreflex responses of adrenal (ASNA), lumbar (LSNA) and renal (RSNA) sympathetic nerve activity

Activation of NTS A1 adenosine receptors evokes differential sympathoactivation (ASNA&gt;RSNA≥LSNA). These responses were attenuated/abolished by sinoaortic denervation plus vagotomy or blockade of glutamatergic transmission in the NTS suggesting that these receptors may inhibit baroreflex transmission in the NTS (Am J Physiol 283: H1588‐99, 2002; 294: H172‐82, 2008). However, potential inhibition of cardiopulmonary chemoreceptors may also contribute to the A1 adenosine‐receptor‐mediated differential regional sympathoactivation. Therefore, in the present study we compared regional sympathoinhibition evoked by right atrial injections of 5HT3 receptor agonist (phenylbiguanide (PBG) 1‐8 μg/kg) before and after stimulation of NTS A1 adenosine receptors (microinjections of CPA, 330 pmol/50 nl) in urethane/chloralose anesthetized rats (n=7). Activation of cardiopulmonary chemoreceptors evoked differential, dose dependent sympathoinhibition (RSNA&gt;ASNA&gt;LSNA). The responses to all doses of PBG (Δ%) were greatly attenuated following stimulation of NTS A1 adenosine receptors (‐95.6±1.2 vs. ‐40.4±8.5, ‐75.4±5.8 vs. ‐27.5±6.8, ‐60.9±3.3 vs. ‐29.1±7.3, for RSNA, ASNA and LSNA respectively at the maximal dose of PBG). We conclude that activation of A1 adenosine receptors in the NTS differentially inhibits the cardiopulmonary chemoreflex responses of regional sympathetic outputs. NIH HL‐67814

Thermoregulatory Responses Induced by Central Cholinergic Stimulation During Exercise Are Mediated By Arterial Baroreceptors.

The aim of this study was to evaluate if the effects of central cholinergic stimulation on thermoregulation during exercise are mediated by arterial baroreceptors. Wistar rats were fitted with cannulae into the lateral cerebral ventricle and subsequently submitted to sinoaortic denervation (Sad) or sham surgery. After two weeks, a catheter was implanted into the ascendant aorta and a thermal sensor into the abdominal cavity. Two days latter they were submitted to exercise on a treadmill at 18 m·min−1 and 5% inclination until fatigue, when tail skin (Ttail) and body temperature (Tb) and pulsatile arterial pressure were measured after the injection of 2 μL of 10 μ 10−3 M physostigmine (Phy) or 0.15 M NaCl solution (Sal) into the cerebral ventricle. Phy‐treated rats had a higher increase in Ttail (30.8 ± 0.6 ºC Phy‐sham vs. 28.0 ± 0.5 ºC Sal‐sham; P&lt;0.05) and lower exercise‐induced increase in Tb (37.9 ± 0.6 ºC Phy‐sham vs. 38.6 ± 1.0 ºC Sal‐sham; P&lt;0.05). In contrast, sinoaortic denervation blunted the Phy injection effects in both Ttail and Tb. Furthermore, Sad rats had a higher increase in Ttail (33.4 ± 0.3 ºC Sad vs. 32.3 ± 0.3 ºC sham; P&lt;0.05) compared with sham group without affecting Tb. We conclude that baroreceptors are involved in thermoregulatory adjustments during exercise. In addition, thermoregulatory responses induced by central cholinergic stimulation during exercise are mediated by arterial baroreceptors.

AT1 receptors in the paraventricular nucleus (PVN) are required for sympathoexcitation due to angiotensin II in the subfornical organ of nonpregnant and pregnant rats.

Activation of AT1 receptors in the subfornical organ (SFO) by circulating angiotensin A II (A II) increases mean arterial pressure (MAP) through a pathway which includes the PVN. A II levels are increased and CNS actions of A II may support sympathetic nerve activity in pregnancy. The role of the PVN, and AT1 receptors in the PVN, in responses to microinjection of A II into the SFO was tested in nonpregnant (NP) and term pregnant (P) rats. In 7 NP and 8 P sinoaortic denervated (SAD) inactin anesthetized rats, baseline mean arterial pressure (MAP) was lower (P= 96 ±5; NP= 120 ±8 mmHg) and heart rate was higher (P =374 ±11; NP =330 ±10 bpm) in P rats. The increase in MAP in response to A II (20 µM, 50 nl) in the SFO was greater in P compared to NP rats (ΔMAP: P = +22 ±3; NP = +14 ±2 mmHg). Bilateral microinjection of the GABAA receptor agonist, muscimol (1.5 mM, 100 nl), into the PVN decreased MAP (ΔMAP: P= ‐43±7 mmHg; NP= ‐46±4 mmHg) and LSNA (ΔLSNA: P= ‐34±13%; NP= ‐37±3%) and eliminated responses to activation of the SFO in both groups. In 3P and 2NP rats AT1 receptor blockade (L158, 809, 20 mM, 100 nl) in the PVN also eliminated responses to activation of the SFO with A II. Thus, AT1 receptors in the PVN are required for sympathoexcitation mediated by SFO A II in both NP and P rats. (NIH HL 36245).