Exercise training enhances baroreflex sensitivity by an angiotensin II-dependent mechanism in chronic heart failure

2008 ◽  
Vol 104 (3) ◽  
pp. 616-624 ◽  
Author(s):  
Tarek M. Mousa ◽  
Dongmei Liu ◽  
Kurtis G. Cornish ◽  
Irving H. Zucker
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Exercise Training ◽  
Sympathetic Nerve ◽  
Baroreflex Sensitivity ◽  
Sympathetic Nerve Activity ◽  
Ang Ii ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Renal Sympathetic

Exercise training (EX) has become an important modality capable of enhancing the quality of life and survival of patients with chronic heart failure (CHF). Although 4 wk of EX in animals with CHF evoked a reduction in renal sympathetic nerve activity and ANG II plasma levels and an enhancement in baroreflex sensitivity at rest (Liu JL, Irvine S, Reid IA, Patel KP, Zucker IH, Circulation 102: 1854–1862, 2000; Liu JL, Kulakofsky J, Zucker IH, J Appl Physiol 92: 2403–2408, 2002), it is unclear whether these phenomena are causally related. CHF was induced in rabbits by ventricular pacing (360–380 beats/min) for 3 wk. CHF rabbits were EX for 4 wk at 15–18 m/min, 6 days/wk, 30–40 min/day. Three groups of rabbits were studied: CHF (with no EX), CHF-EX, and CHF-EX + ANG II infusion [in which ANG II levels were kept at or near levels observed in CHF (non-EX) rabbits by subcutaneous osmotic minipump infusion]. EX prevented the increase in plasma ANG II levels shown in CHF rabbits. CHF and CHF-EX + ANG II infusion rabbits had significantly depressed baroreflex sensitivity slopes ( P < 0.01 for sodium nitroprusside and P < 0.001 for phenylephrine) and higher baseline renal sympathetic nerve activities than CHF-EX animals. EX downregulated mRNA and protein expression of ANG II type 1 receptors in the rostral ventrolateral medulla in CHF rabbits. This was prevented by ANG II infusion. These data are consistent with the view that the reduction in sympathetic nerve activity and the improvement in baroreflex function in CHF after EX are due to the concomitant reduction in ANG II and angiotensin receptors in the central nervous system.

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.

scholarly journals Chronic AT1 receptor blockade normalizes NMDA-mediated changes in renal sympathetic nerve activity and NR1 expression within the PVN in rats with heart failure

2010 ◽  
Vol 298 (5) ◽  
pp. H1546-H1555 ◽  
Author(s):  
Allison C. Kleiber ◽  
Hong Zheng ◽  
Neeru M. Sharma ◽  
Kaushik P. Patel
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Protein Expression ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic

Exercise training normalizes enhanced glutamatergic mechanisms within the paraventricular nucleus (PVN) concomitant with the normalization of increased plasma ANG II levels in rats with heart failure (HF). We tested whether ANG II type 1 (AT1) receptors are involved in the normalization of PVN glutamatergic mechanisms using chronic AT1 receptor blockade with losartan (Los; 50 mg·kg−1·day−1 in drinking water for 3 wk). Left ventricular end-diastolic pressure was increased in both HF + vehicle (Veh) and HF + Los groups compared with sham-operated animals (Sham group), although it was significantly attenuated in the HF + Los group compared with the HF + Veh group. The effect of Los on cardiac function was similar to exercise training. At the highest dose of N-methyl-d-aspartate (NMDA; 200 pmol) injected into the PVN, the increase in renal sympathetic nerve activity was 93 ± 13% in the HF + Veh group, which was significantly higher ( P < 0.05) than the increase in the Sham + Veh (45 ± 2%) and HF + Los (47 ± 2%) groups. Relative NMDA receptor subunit NR1 mRNA expression within the PVN was increased 120% in the HF + Veh group compared with the Sham + Veh group ( P < 0.05) but was significantly attenuated in the HF + Los group compared with the HF + Veh group ( P < 0.05). NR1 protein expression increased 87% in the HF + Veh group compared with the Sham + Veh group but was significantly attenuated in the HF + Los group compared with the HF + Veh group ( P < 0.05). Furthermore, in in vitro experiments using neuronal NG-108 cells, we found that ANG II treatment stimulated NR1 protein expression and that Los significantly ameliorated the NR1 expression induced by ANG II. These data are consistent with our hypothesis that chronic AT1 receptor blockade normalizes glutamatergic mechanisms within the PVN in rats with HF.

scholarly journals Angiotensin receptor antagonist improves cardiac reflex control of renal sodium handling in heart failure

1998 ◽  
Vol 274 (2) ◽  
pp. H636-H641 ◽  
Author(s):  
Gerald F. Dibona ◽  
Susan Y. Jones ◽  
Linda L. Sawin
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Right Atrial ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Renal Sodium Handling ◽  
Renal Sympathetic

In rats with congestive heart failure, type 1 angiotensin II receptor antagonist treatment (losartan) decreases basal renal sympathetic nerve activity and improves arterial baroreflex regulation of renal sympathetic nerve activity. This investigation examined the effect of losartan on cardiac baroreflex regulation of renal sympathetic nerve activity and renal sodium handling in rats with congestive heart failure. Losartan treatment decreased arterial pressure from 120 ± 3 to 93 ± 5 mmHg and increased the afferent (from 0.95 ± 0.21 to 2.22 ± 0.42% Δafferent vagal nerve activity/mmHg mean right atrial pressure, P < 0.05) and overall gain (from −1.14 ± 0.19 to −4.20 ± 0.39% Δrenal sympathetic nerve activity/mmHg mean right atrial pressure, P < 0.05) of the cardiac baroreflex. During isotonic saline volume loading, urinary sodium excretion increased from 2.4 ± 0.8 to 10.5 ± 1.3 μeq/min in vehicle-treated rats (excretion of 52 ± 3% of the load) and from 3.0 ± 1.0 to 15.1 ± 1.8 μeq/min in losartan-treated rats (excretion of 65 ± 4% of the load, P < 0.05). When rats were changed from a low- to a high-sodium diet, cumulative sodium balance over 5 days was 7.8 ± 0.6 meq in vehicle-treated rats and 4.2 ± 0.4 meq in losartan-treated rats ( P < 0.05). In congestive heart failure, losartan treatment improved cardiac baroreflex regulation of renal sympathetic nerve activity, which was associated with improved ability to excrete acute and chronic sodium loads.

scholarly journals Responses mediated by the RVLM on splancnic and renal sympathetic nerve activity in heart failure rats

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Bruno Arruda Carillo ◽  
Paulo J.F Tucci ◽  
Ednei L Antonio ◽  
Alexandra A Santos ◽  
Cassia T Bergamaschi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Renal Sympathetic

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.

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