Microinjection of ANG II into paraventricular nucleus enhances cardiac sympathetic afferent reflex in rats

2002 ◽  
Vol 282 (6) ◽  
pp. H2039-H2045 ◽  
Author(s):  
Guo-Qing Zhu ◽  
Kuashik P. Patel ◽  
Irving H. Zucker ◽  
Wei Wang
Keyword(s):  
Electrical Stimulation ◽  
Paraventricular Nucleus ◽  
Sympathetic Nerve Activity ◽  
Sympathetic Nerves ◽  
Ang Ii ◽  
Renal Sympathetic Nerve Activity ◽  
Afferent Nerves ◽  
Cardiac Sympathetic Afferent Reflex ◽  
Renal Sympathetic

The aims of present study were to determine whether angiotensin II (ANG II) in the paraventricular nucleus (PVN) is involved in the central integration of the cardiac sympathetic afferent reflex and whether this effect is mediated by the ANG type 1 (AT1) receptor. While the animals were under α-chloralose and urethane anesthesia, mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) were recorded in sinoaortic-denervated and cervical-vagotomized rats. A cannula was inserted into the left PVN for microinjection of ANG II. The cardiac sympathetic afferent reflex was tested by electrical stimulation (5, 10, 20, and 30 Hz in 10 V and 1 ms) of the afferent cardiac sympathetic nerves or epicardial application of bradykinin (BK) (0.04 and 0.4 μg in 2 μl). Microinjection of ANG II (0.03, 0.3, and 3 nmol) into the PVN resulted in dose-related increases in the RSNA responses to electrical stimulation. The percent change of RSNA response to 20- and 30-Hz stimulation increased significantly at the highest dose of ANG II (3 nmol). The effects of ANG II were prevented by pretreatment with losartan (50 nmol) into the PVN. Microinjection of ANG II (0.3 nmol) into the PVN significantly enhanced the RSNA responses to epicardial application of BK, which was abolished by pretreatment with losartan (50 nmol) into the PVN. These results suggest that exogenous ANG II in the PVN augments the cardiac sympathetic afferent reflex evoked by both electrical stimulation of cardiac sympathetic afferent nerves and epicardial application of BK. These central effects of ANG II are mediated by AT1 receptors.

ANG II in the paraventricular nucleus potentiates the cardiac sympathetic afferent reflex in rats with heart failure

2004 ◽  
Vol 97 (5) ◽  
pp. 1746-1754 ◽  
Author(s):  
Guo-Qing Zhu ◽  
Lie Gao ◽  
Kuashik P. Patel ◽  
Irving H. Zucker ◽  
Wei Wang
Keyword(s):  
Heart Failure ◽  
Electrical Stimulation ◽  
Paraventricular Nucleus ◽  
Sham Group ◽  
Ang Ii ◽  
Renal Sympathetic Nerve Activity ◽  
Afferent Nerves ◽  
Coronary Ligation ◽  
Cardiac Sympathetic Afferent Reflex ◽  
Renal Sympathetic

Chronic heart failure (CHF) is characterized by sympathoexcitation, and the cardiac sympathetic afferent reflex (CSAR) is a sympathoexcitatory reflex. Our previous studies have shown that the CSAR was enhanced in CHF. In addition, central angiotensin II (ANG II) is an important modulator of this reflex. This study was performed to determine whether the CSAR evoked by stimulation of cardiac sympathetic afferent nerves (CSAN) in rats with coronary ligation-induced CHF is enhanced by ANG II in the paraventricular nucleus (PVN). Under α-chloralose and urethane anesthesia, renal sympathetic nerve activity (RSNA) was recorded. The RSNA responses to electrical stimulation (5, 10, 20, and 30 Hz) of the CSAN were evaluated. Bilateral microinjection of the AT1-receptor antagonist losartan (50 nmol) into the PVN had no significant effects in the sham group, but it abolished the enhanced RSNA response to stimulation in the CHF group. Unilateral microinjection of three doses of ANG II (0.03, 0.3, and 3 nmol) into the PVN resulted in dose-related increases in the RSNA responses to stimulation. Although ANG II also potentiated the RSNA response to electrical stimulation in sham rats, the RSNA responses to stimulation after ANG II into the PVN in rats with CHF were much greater than in sham rats. The effects of ANG II were prevented by pretreatment with losartan into the PVN in CHF rats. These results suggest that the central gain of the CSAR is enhanced in rats with coronary ligation-induced CHF and that ANG II in the PVN augments the CSAR evoked by CSAN, which is mediated by the central angiotensin AT1 receptors in rats with CHF.

Chronic central infusion of ANG II potentiates cardiac sympathetic afferent reflex in dogs

1999 ◽  
Vol 277 (1) ◽  
pp. H15-H22 ◽  
Author(s):  
Rong Ma ◽  
Harold D. Schultz ◽  
Wei Wang
Keyword(s):  
Sympathetic Nerve Activity ◽  
Central Effect ◽  
Ang Ii ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Intracerebroventricular Infusion ◽  
Afferent Nerves ◽  
Cardiac Sympathetic Afferent Reflex ◽  
Renal Sympathetic ◽  
Stimulation Of

The aims of this study were to determine whether ANG II is involved in the central integration of the cardiac sympathetic afferent reflex (CSAR), and if this central effect of ANG II is mediated by the AT1 receptor. Experiments were undertaken in dogs that were anesthetized with α-chloralose, sinoaortic denervated, and vagotomized. The renal sympathetic nerve activity (RSNA) responses to varying frequency and voltage stimulation of cardiac sympathetic afferent nerves were used to evaluate the central sensitivity of the CSAR. In two groups of dogs, two doses (50 and 100 ng/min icv) of ANG II were acutely infused. In a third group of dogs, ANG II was chronically infused for 3 days (100 ng/min, 1 μl/h icv). We found that acute infusion into the cerebroventricle of two doses of ANG II did not affect the central sensitivity of the CSAR or the baseline hemodynamics, but the baseline RSNA increased significantly during the infusion of the higher dose of ANG II. However, chronic intracerebroventricular infusion of ANG II enhanced the central sensitivity of the CSAR significantly. In addition, chronic intracerebrovetricular infusion of ANG II elicited a significant increase in water intake and in arterial pressure from the first and second day of infusion, respectively. In the group that received chronic intracerebroventricular infusion of ANG II, the administration of an AT1-receptor antagonist losartan (0.125 mg/kg icv) abolished ANG II-induced augmentation of the CSAR. These results suggest that chronic elevation of central ANG II can sensitize the CSAR via central AT1 receptors.

scholarly journals Enhanced angiotensin-mediated excitation of renal sympathetic nerve activity within the paraventricular nucleus of anesthetized rats with heart failure

2009 ◽  
Vol 297 (5) ◽  
pp. R1364-R1374 ◽  
Author(s):  
Hong Zheng ◽  
Yi-Fan Li ◽  
Wei Wang ◽  
Kaushik P. Patel
Keyword(s):  
Heart Failure ◽  
Paraventricular Nucleus ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Receptor Expression ◽  
Ang Ii ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Renal Sympathetic

Chronic heart failure (HF) is characterized by increased sympathetic drive. Enhanced angiotensin II (ANG II) activity may contribute to the increased sympathoexcitation under HF condition. The present study examined sympathoexcitation by 1) the effects of ANG II in the paraventricular nucleus (PVN) on renal sympathetic nerve activity (RSNA), and 2) the altered ANG II type 1 (AT1) receptor expression during HF. Left coronary artery ligation was used to induce HF. In the anesthetized Sprague-Dawley rats, microinjection of ANG II (0.05–1 nmol) into the PVN increased RSNA, mean arterial pressure (MAP), and heart rate (HR) in both sham-operated and HF rats. The responses of RSNA and HR were significantly enhanced in rats with HF compared with sham rats (RSNA: 64 ± 8% vs. 33 ± 4%, P < 0.05). Microinjection of AT1 receptor antagonist losartan into the PVN produced a decrease of RSNA, MAP, and HR in both sham and HF rats. The RSNA and HR responses to losartan in HF rats were significantly greater (RSNA: −25 ± 4% vs. −13 ± 1%, P < 0.05). Using RT-PCR and Western blot analysis, we found that there were significant increases in the AT1 receptor mRNA (Δ186 ± 39%) and protein levels (Δ88 ± 20%) in the PVN of rats with HF ( P < 0.05). The immunofluorescence of AT1 receptors was significantly higher in the PVN of rats with HF. These data support the conclusion that an increased angiotensinergic activity on sympathetic regulation, due to the upregulation of ANG II AT1 receptors within the PVN, may contribute to the elevated sympathoexcitation that is observed during HF.

Central gain of the cardiac sympathetic afferent reflex in dogs with heart failure

1997 ◽  
Vol 273 (6) ◽  
pp. H2664-H2671 ◽  
Author(s):  
Rong Ma ◽  
Irving H. Zucker ◽  
Wei Wang
Keyword(s):  
Heart Failure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Sympathetic Nerves ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Failure Group ◽  
Renal Sympathetic Nerve ◽  
Cardiac Sympathetic Afferent Reflex ◽  
Renal Sympathetic

Previous studies from our laboratory have shown that the cardiac sympathetic afferent reflex is enhanced in dogs with experimental heart failure. The aim of the present study was to determine if the central gain of the cardiac sympathetic afferent reflex was also enhanced in dogs with heart failure. Fifteen dogs with pacing-induced heart failure were used in this study. Seventeen sham-operated dogs served as control. At the time of the acute experiment the dogs were anesthetized with α-chloralose. Arterial blood pressure, heart rate, and renal sympathetic nerve activity were recorded. After sinoaortic denervation and cervical vagotomy, a thoracotomy was performed in the second intercostal space. The left stellate ganglion was identified, and the left cardiac sympathetic nerves were cut. The central end of the left cardiac sympathetic nerves was placed on bipolar stimulating electrodes. The renal sympathetic nerve activity responses to electrical stimulation (30 Hz, 1 ms with varying voltages from 1 to 10 V; or 10 V, 1 ms with varying frequencies from 1 to 30 Hz) of the afferent cardiac sympathetic nerves were compared between sham and heart failure groups. Reflex renal sympathetic nerve activity responses to stimulation of the cardiac sympathetic nerves were significantly greater in the heart failure group compared with that in the sham group (21.4 ± 3.2 vs. 9.8 ± 2.9% at 10 V, 30 Hz and 27.7 ± 4.5 vs. 9.9 ± 3.4% at 30 Hz, 10 V, heart failure vs. sham group, respectively; for both relationships, P < 0.05). This enhanced central gain of the cardiac sympathetic afferent reflex in the heart failure group was significantly attenuated after intravenous and cerebroventricular injection of the angiotensin II receptor antagonist losartan (5 mg/kg iv and 0.125 mg/kg in 0.1 ml icv). These data suggest that the central gain of the cardiac sympathetic afferent reflex is enhanced in dogs with heart failure and central angiotensin II plays an important role in this enhanced response.

Interactions between ANP and ANG II in regulating blood pressure and sympathetic outflow

1991 ◽  
Vol 260 (6) ◽  
pp. R1145-R1151 ◽  
Author(s):  
M. K. Steele ◽  
D. G. Gardner ◽  
P. L. Xie ◽  
H. D. Schultz
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve Activity ◽  
Ang Ii ◽  
Contrast Injection ◽  
Synthesis Inhibitor ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Arterial Blood ◽  
Pressor Responses ◽  
Renal Sympathetic

In anesthetized rats with sinoaortic denervation, intracerebroventricular (icv) injection of atrial natriuretic peptide (ANP) resulted in decreased mean arterial blood pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) (depressor effects), whereas icv angiotensin II (ANG II) produced increases in these variables (pressor effects). The depressor effects of ANP were slower in onset and longer in duration than the pressor effects of ANG II. Intracerebroventricular injection of the ANG II-receptor blocker sarthran or the ANG II-synthesis inhibitor captopril resulted in a significant reduction in MAP; HR and RSNA were not affected. Both sarthran and captopril abolished the depressor responses to icv ANP. In contrast, injection of an anti-rat ANP antibody, which blocked the depressor effects of icv ANP, did not by itself modify MAP, HR, or RSNA, nor did the antibody affect the pressor responses to icv ANG II. These data suggest that, in this animal model, the depressor effects of icv ANP are mediated by the inhibition of brain ANG II-dependent neural activity. These results also demonstrate that, in this preparation, the endogenous ANG II system actively contributes to the maintenance of basal MAP, whereas the central ANP system, at least in regions accessible to the antirat ANP antibody, plays little role in this maintenance.

AT1-receptor blockade in the hypothalamic PVN reduces central hyperosmolality-induced renal sympathoexcitation

2001 ◽  
Vol 281 (6) ◽  
pp. R1844-R1853 ◽  
Author(s):  
Qing Hui Chen ◽  
Glenn M. Toney
Keyword(s):  
Sympathetic Nerve Activity ◽  
Internal Carotid ◽  
Receptor Activation ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Autonomic Neurons ◽  
Osmotic Challenge ◽  
Renal Sympathetic

Autonomic neurons in the hypothalamic paraventricular nucleus (PVN) are innervated by osmotic-sensitive regions of the lamina terminalis, receive input from ANG II-containing cells, and express AT1 ANG II receptors. Therefore, we hypothesized that ANG II actions within the PVN could underlie hyperosmolality-induced increases in renal sympathetic nerve activity (RSNA). In anesthetized baroreceptor-denervated rats, graded concentrations of NaCl (0.30, 0.9, 1.5, and 2.1 osmol/l) were injected (300 μl) centrally via the internal carotid artery (ICA) and produced corresponding increases in mean arterial pressure (MAP) and RSNA. In addition, equivalent hyperosmotic loads (1.5 osmol/l) of NaCl, glucose, and mannitol each significantly ( P < 0.05) increased MAP and RSNA. The same stimuli had no effect when administered intravenously. Bilateral PVN microinjections (100 nl) of the AT1-receptor antagonist losartan (80 nmol) before osmotic challenge had no effect on resting RSNA but significantly ( P < 0.05) reduced RSNA responses to hyperosmotic NaCl ( n = 7), glucose ( n = 6), and mannitol ( n = 6). Increases in RSNA evoked by hyperosmotic NaCl were significantly ( P < 0.05) attenuated ∼20 min after losartan injection and recovered within 60–120 min. In contrast, losartan outside the PVN as well as vehicle (saline) within the PVN failed to alter RSNA responses to ICA hyperosmotic NaCl. Results suggest that elevated RSNA after central sodium/osmotic activation is mediated, at least in part, by a synaptic mechanism involving AT1-receptor activation within the PVN.

Angiotensin II acutely attenuates range of arterial baroreflex control of renal sympathetic nerve activity

2000 ◽  
Vol 279 (4) ◽  
pp. H1804-H1812 ◽  
Author(s):  
Max G. Sanderford ◽  
Vernon S. Bishop
Keyword(s):  
Angiotensin Ii ◽  
Sympathetic Nerve ◽  
Intravenous Infusion ◽  
Sympathetic Nerve Activity ◽  
Ang Ii ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Arterial Blood ◽  
Renal Sympathetic

Acutely increasing peripheral angiotensin II (ANG II) reduces the maximum renal sympathetic nerve activity (RSNA) observed at low mean arterial blood pressures (MAPs). We postulated that this observation could be explained by the action of ANG II to acutely increase arterial blood pressure or increase circulating arginine vasopressin (AVP). Sustained increases in MAP and increases in circulating AVP have previously been shown to attenuate maximum RSNA at low MAP. In conscious rabbits pretreated with an AVP V1 receptor antagonist, we compared the effect of a 5-min intravenous infusion of ANG II (10 and 20 ng · kg−1 · min−1) on the relationship between MAP and RSNA when the acute pressor action of ANG II was left unopposed with that when the acute pressor action of ANG II was opposed by a simultaneous infusion of sodium nitroprusside (SNP). Intravenous infusion of ANG II resulted in a dose-related attenuation of the maximum RSNA observed at low MAP. When the acute pressor action of ANG II was prevented by SNP, maximum RSNA at low MAP was attenuated, similar to that observed when ANG II acutely increased MAP. In contrast, intravertebral infusion of ANG II attenuated maximum RSNA at low MAP significantly more than when administered intravenously. The results of this study suggest that ANG II may act within the central nervous system to acutely attenuate the maximum RSNA observed at low MAP.

Central sympathoinhibition and peripheral neuronal uptake blockade after desipramine in rabbits

1991 ◽  
Vol 260 (4) ◽  
pp. R824-R832 ◽  
Author(s):  
G. Eisenhofer ◽  
T. Saigusa ◽  
M. D. Esler ◽  
H. S. Cox ◽  
J. A. Angus ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve Activity ◽  
Sympathetic Nerves ◽  
Neuronal Uptake ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Mediated Effects ◽  
Before And After ◽  
Peripheral Effect ◽  
Renal Sympathetic

Peripheral- and central nervous system (CNS)-mediated effects of desipramine (Des) on sympathetic nerves and the contribution of alpha 2-adrenoceptors to these effects were studied in conscious rabbits. Blood pressure, renal sympathetic nerve activity (SNA), and norepinephrine (NE) reuptake and spillover into plasma were measured before and after intracisternal (ic) or intravenous (i.v.) administration of Des. In other animals, NE spillover responses to i.v. Des were examined before and after alpha 2-adrenoceptor blockade with i.v. idazoxan. Treatment with i.v. Des blocked neuronal reuptake and decreased renal SNA but did not alter blood pressure or NE spillover. Decreased NE release by sympathetic nerves after i.v. Des was reflected by a decrease in the combined rate of NE reuptake and spillover. Treatment with ic Des (at 1.7% of the i.v. dose) decreased blood pressure and renal SNA and produced equivalent falls in NE reuptake and spillover, indicating little peripheral effect of centrally administered Des on the efficiency of neuronal reuptake. Thus Des had two distinct actions: the drug blocked neuronal reuptake by direct actions on nerve endings and reduced SNA by actions within the CNS. After ic Des, decreased SNA produced parallel falls in NE reuptake, spillover, and blood pressure. After i.v. Des, blockade of neurotransmitter reuptake increased NE concentrations at sympathoeffector junctions offsetting the fall in SNA, so that there was little change in NE spillover or blood pressure. However, after alpha 2-adrenoceptor blockade with i.v. idazoxan, NE spillover increased in response to i.v. Des. Thus the Des-induced decrease in NE release was partly mediated by an action of raised intrasynaptic NE concentrations on inhibitory alpha 2-adrenoceptors.

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