scholarly journals Central Ang II (Angiotensin II)-Mediated Sympathoexcitation

Hypertension ◽  
2021 ◽  
Vol 77 (1) ◽  
pp. 147-157
Author(s):  
Neeru M. Sharma ◽  
Andréa S. Haibara ◽  
Kenichi Katsurada ◽  
Shyam S. Nandi ◽  
Xuefei Liu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Sympathetic Tone ◽  
Sympathetic Outflow ◽  
Ang Ii ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Renal Sympathetic

Central infusion of Ang II (angiotensin II) has been associated with increased sympathetic outflow resulting in neurogenic hypertension. In the present study, we appraised whether the chronic increase in central Ang II activates the paraventricular nucleus of the hypothalamus (PVN) resulting in elevated sympathetic tone and altered baro- and chemoreflexes. Further, we evaluated the contribution of HIF-1α (hypoxia-inducible factor-1α), a transcription factor involved in enhancing the expression of N-methyl-D-aspartate receptors and thus glutamatergic-mediated sympathetic tone from the PVN. Ang II infusion (20 ng/minute, intracerebroventricular, 14 days) increased mean arterial pressure (126±9 versus 84±4 mm Hg), cardiac sympathetic tone (96±7 versus 75±6 bpm), and decreased cardiac parasympathetic tone (16±2 versus 36±3 versus bpm) compared with saline-infused controls in conscious rats. The Ang II-infused group also showed an impaired baroreflex control of heart rate (−1.50±0.1 versus −2.50±0.3 bpm/mm Hg), potentiation of the chemoreflex pressor response (53±7 versus 30±7 mm Hg) and increased number of FosB-labeled cells (53±3 versus 19±4) in the PVN. Concomitant with the activation of the PVN, there was an increased expression of HIF-1α and N-Methyl-D-Aspartate-type1 receptors in the PVN. Further, Ang II-infusion showed increased renal sympathetic nerve activity (20.5±2.3% versus 6.4±1.9% of Max) and 3-fold enhanced renal sympathetic nerve activity responses to microinjection of N-methyl-D-aspartate (200 pmol) into the PVN of anesthetized rats. Further, silencing of HIF-1α in NG108 cells abrogated the expression of N-methyl-D-aspartate-N-methyl-D-aspartate-type1 induced by Ang II. Taken together, our studies suggest a novel Ang II-HIF-1α-N-methyl-D-aspartate receptor-mediated activation of preautonomic neurons in the PVN, resulting in increased sympathetic outflow and alterations in baro- and chemoreflexes.

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.

NO and endogenous angiotensin II interact in the generation of renal sympathetic nerve activity in conscious rats

2004 ◽  
Vol 286 (4) ◽  
pp. H1258-H1265 ◽  
Author(s):  
Donogh F. McKeogh ◽  
Theresa L. O'Donaughy ◽  
Virginia L. Brooks
Keyword(s):  
Angiotensin Ii ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Ang Ii ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Conscious Rats ◽  
Renal Sympathetic Nerve ◽  
Low Sodium ◽  
Renal Sympathetic

Nitric oxide (NO) appears to inhibit sympathetic tone in anesthetized rats. However, whether NO tonically inhibits sympathetic outflow, or whether endogenous angiotensin II (ANG II) promotes NO-mediated sympathoinhibition in conscious rats is unknown. To address these questions, we determined the effects of NO synthase (NOS) inhibition on renal sympathetic nerve activity (RSNA) and heart rate (HR) in conscious, unrestrained rats on normal (NS), high-(HS), and low-sodium (LS) diets, in the presence and absence of an ANG II receptor antagonist (AIIRA). When arterial pressure was kept at baseline with intravenous hydralazine, NOS inhibition with l-NAME (10 mg/kg iv) resulted in a profound decline in RSNA, to 42 ± 11% of control ( P < 0.01), in NS animals. This effect was not sustained, and RSNA returned to control levels by 45 min postinfusion. l-NAME also caused bradycardia, from 432 ± 23 to 372 ± 11 beats/min postinfusion ( P < 0.01), an effect, which, in contrast, was sustained 60 min postdrug. The effects of NOS inhibition on RSNA and HR did not differ between NS, HS, and LS rats. However, when LS and HS rats were pretreated with AIIRA, the initial decrease in RSNA after l-NAME infusion was absent in the LS rats, while the response in the HS group was unchanged by AIIRA. These findings indicate that, in contrast to our hypotheses, NOS activity provides a stimulatory input to RSNA in conscious rats, and that in LS animals, but not HS animals, this sympathoexcitatory effect of NO is dependent on the action of endogenous ANG II.

Mechano- and chemoreceptor modulation of renal sympathetic nerve activity at birth in fetal sheep

1999 ◽  
Vol 276 (5) ◽  
pp. R1295-R1301 ◽  
Author(s):  
Jeffrey L. Segar ◽  
Oliva J. Smith ◽  
Aaron T. Holley
Keyword(s):  
Blood Pressure ◽  
Cesarean Section ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Afferent Input ◽  
Ang Ii ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Renal Sympathetic

Physiological responses at birth include increases in heart rate (HR), blood pressure, sympathetic nerve activity, and circulating vasoactive peptides. The factors mediating these responses are not known. To test the hypothesis that afferent input from peripheral mechanoreceptors (arterial and cardiopulmonary baroreceptors) and chemoreceptors contribute to the sympathoexcitatory and hormonal responses at birth, we studied the effects of sinoaortic denervation (SAD) and SAD with vagotomy (Vx) on changes in HR, mean arterial blood pressure (MABP), renal sympathetic nerve activity (RSNA), and catecholamine, arginine vasopressin (AVP), and ANG II levels at birth in term sheep. One hour after delivery by cesarean section, RSNA increased by 168 ± 49 and 192 ± 32% (relative to fetal values) in SAD and SAD-Vx animals, respectively. Significant increases in HR (18 ± 5 and 20 ± 6%) and MABP (24 ± 4 and 20 ± 5%) were also observed 1 h after delivery in SAD and SAD-Vx lambs, respectively. These responses are similar to those seen in intact sheep delivered at the same gestational age. AVP levels markedly increased after birth (19.8 ± 6.7 to 136.1 ± 75.9 pg/ml) in SAD-Vx lambs, whereas SAD animals displayed no change in AVP concentrations. Plasma ANG II also did not change after birth in either group, although levels were consistently higher ( P < 0.01) in SAD compared with SAD-Vx animals. In the presence of SAD, Vx resulted in significantly greater plasma levels of norepinephrine, although levels did not change after birth in either group. The epinephrine responses at birth were similar in both groups of animals. The present data suggest that afferent input from peripheral chemoreceptors and mechanoreceptors contributes little to the hemodynamic and sympathetic responses after delivery by cesarean section. On the other hand, these peripheral mechanisms appear to be involved in modulating endocrine responses at birth.

NMDA-mediated increase in renal sympathetic nerve discharge within the PVN: role of nitric oxide

2001 ◽  
Vol 281 (6) ◽  
pp. H2328-H2336 ◽  
Author(s):  
Yi-Fan Li ◽  
William G. Mayhan ◽  
Kaushik P. Patel
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Dependent Manner ◽  
Sympathetic Outflow ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Dose Dependent ◽  
Renal Sympathetic ◽  
Nerve Discharge

The paraventricular nucleus (PVN) of the hypothalamus is an important site of integration in the central nervous system for sympathetic outflow. Both glutamate and nitric oxide (NO) play an important role in the regulation of sympathetic nerve activity. The purpose of the present study was to examine the interaction of NO and glutamate within the PVN in the regulation of renal sympathetic nerve activity in rats. Renal sympathetic nerve discharge (RSND), arterial blood pressure (BP), and heart rate (HR) were measured in response to administration of N-methyl-d-aspartic acid (NMDA) and N G-monomethyl-l-arginine (l-NMMA) into the PVN. We found that microinjection of NMDA (25, 50, and 100 pmol) into the PVN increased RSND, BP, and HR in a dose-dependent manner, reaching 53 ± 9%, 19 ± 3 mmHg, and 32 ± 12 beats/min, respectively, at the highest dose. These responses were significantly enhanced by prior microinjection ofl-NMMA. On the other hand, inhibition of NO within the PVN by microinjection of l-NMMA also induced increases in RSND, BP, and HR in a dose-dependent manner, reaching 48 ± 6.5%, 11 ± 4 mmHg, and 55 ± 16 beats/min, respectively, at the highest dose. This sympathoexcitatory response was eliminated by prior microinjection of dl-2-amino-5-phosphonovaleric acid, an antagonist of the NMDA receptor. Furthermore, with the use of the push-pull technique, perfusion of glutamate (0.5 μmol) or NMDA (0.1 nmol) into the PVN induced an increase in NO release. In conclusion, our data indicate that NMDA receptors within the PVN mediate an excitatory effect on renal sympathetic nerve activity, arterial BP, and HR. NO in the PVN, which is released by activation of the NMDA receptor, also inhibits NMDA-mediated increases in sympathetic nerve activity. This negative feedback of NO on the glutamate system within the PVN may play an important role in maintaining the overall balance and tone of sympathetic outflow in normal and pathophysiological conditions known to have increased sympathetic tone.

Baroreflexes prevent neurally induced sodium retention in angiotensin hypertension

2000 ◽  
Vol 279 (4) ◽  
pp. R1437-R1448 ◽  
Author(s):  
Thomas E. Lohmeier ◽  
Justin R. Lohmeier ◽  
Atif Haque ◽  
Drew A. Hildebrandt
Keyword(s):  
Sympathetic Nerve ◽  
Sodium Excretion ◽  
Sympathetic Nerve Activity ◽  
Urinary Sodium Excretion ◽  
Sodium Retention ◽  
Ang Ii ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Renal Sympathetic

Recent studies indicate that renal sympathetic nerve activity is chronically suppressed during ANG II hypertension. To determine whether cardiopulmonary reflexes and/or arterial baroreflexes mediate this chronic renal sympathoinhibition, experiments were conducted in conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated (Den) and innervated (Inn) kidneys. Dogs were studied 1) intact, 2) after thoracic vagal stripping to eliminate afferents from cardiopulmonary and aortic receptors [cardiopulmonary denervation (CPD)], and 3) after subsequent denervation of the carotid sinuses to achieve CPD plus complete sinoaortic denervation (CPD + SAD). After control measurements, ANG II was infused for 5 days at a rate of 5 ng · kg−1 · min−1. In the intact state, 24-h control values for mean arterial pressure (MAP) and the ratio for urinary sodium excretion from Den and Inn kidneys (Den/Inn) were 98 ± 4 mmHg and 1.04 ± 0.04, respectively. ANG II caused sodium retention and a sustained increase in MAP of 30–35 mmHg. Throughout ANG II infusion, there was a greater rate of sodium excretion from Inn vs. Den kidneys ( day 5 Den/Inn sodium = 0.51 ± 0.05), indicating chronic suppression of renal sympathetic nerve activity. CPD and CPD + SAD had little or no influence on baseline values for either MAP or the Den/Inn sodium, nor did they alter the severity of ANG II hypertension. However, CPD totally abolished the fall in the Den/Inn sodium in response to ANG II. Furthermore, after CPD + SAD, there was a lower, rather than a higher, rate of sodium excretion from Inn vs. Den kidneys during ANG II infusion ( day 5 Den/Inn sodium = 2.02 ± 0.14). These data suggest that cardiac and/or arterial baroreflexes chronically inhibit renal sympathetic nerve activity during ANG II hypertension and that in the absence of these reflexes, ANG II has sustained renal sympathoexcitatory effects.

Effects of sympathetic nerves and angiotensin II on renal sodium and water handling in rats with common bile duct ligature

2005 ◽  
Vol 288 (6) ◽  
pp. F1267-F1275 ◽  
Author(s):  
Roland Veelken ◽  
Karl F. Hilgers ◽  
Markus Porst ◽  
Holger Krause ◽  
Andrea Hartner ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Sympathetic Nerve ◽  
Renal Denervation ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Volume Load ◽  
Volume Retention ◽  
Renal Sympathetic

We tested the hypothesis that angiotensin II is likely to be mandatory for the neurogenic sodium and volume retention in cirrhotic rats with common bile duct ligature (BDL) following an acute volume load. To assess the neural control of volume homeostasis, 21 days after common BDL rats underwent volume expansion (0.9% NaCL; 10% body wt over 30 min) to decrease renal sympathetic nerve activity. Untreated animals, rats with renal denervation or pretreated with a nonhypotensive dose of an angiotensin II type 1 receptor antagonist were studied. The renal renin-angiotensin system was assessed by immunohistochemistry and RT-PCR. Rats with BDL excreted only 71 ± 4% of the administered volume load. In cirrhotic rats pretreated with an angiotensin II AT1 inhibitor or after renal denervation, these values ranged significantly higher from 98 to 103% ( P < 0.05 for all comparisons). Renal sympathetic nerve activity decreases by volume expansion were impaired in BDL rats ( P < 0.05) but unaffected by angiotensin II receptor inhibition. In kidneys of BDL animals, renin mRNA was increased, and immunohistochemistry revealed increased staining for peritubular angiotensin II. Renal denervation in BDL animals reduced renin expression within 5 days to control levels. In conclusion, the impaired excretion of an acute volume load in rats with liver cirrhosis is due to effects of an increased renal sympathetic nerve activity that are likely to be dependent on intrarenal angiotensin II and renin. We speculate that similar changes may contribute to long-term volume retention in liver cirrhosis.

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