Exercise training reduces sympathetic nerve activity in heart failure patients treated with carvedilol

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.

Download Full-text

Oxygen flow rate affects the apnea index and nocturnal sympathetic nerve activity in heart failure patients with Cheyne-Stokes respiration

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2004.08.132 ◽

2004 ◽

Vol 10 (5) ◽

pp. S188

Author(s):

Usui Yasuhiro ◽

Takata Yoshifumi ◽

Asano Kihiro ◽

Shiina Kazuki ◽

Hirayama Yoji ◽

...

Keyword(s):

Heart Failure ◽

Flow Rate ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Oxygen Flow Rate ◽

Oxygen Flow ◽

Nerve Activity ◽

Heart Failure Patients

Download Full-text

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

Journal of Applied Physiology ◽

10.1152/japplphysiol.00601.2007 ◽

2008 ◽

Vol 104 (3) ◽

pp. 616-624 ◽

Cited By ~ 54

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.

Download Full-text