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Am J Physiol Heart Circ Physiol (January 14, 2005). doi:10.1152/ajpheart.00473.2004
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Submitted on May 20, 2004
Accepted on December 29, 2004

Exercise training improves endogenous nitric oxide mechanims within the paraventricular nucleus in rats with heart failure

Hong Zheng1, Yi-Fan Li1, Kurt G Cornish1, Irving H Zucker1, and Kaushik P Patel1*

1 Physiology and Biophysics, University of Nebraska Medical Center, Omaha, NE, USA

* To whom correspondence should be addressed. E-mail: kpatel{at}unmc.edu.

Previously, we have demonstrated that an altered endogenous nitric oxide (NO) mechanism within the paraventricular nucleus (PVN) contributes to increased renal sympathetic nerve activity (RSNA) in heart failure (HF) rats. The goal of this study was to examine the effect of exercise training (ExT) in improving the endogenous NO mechanism within the PVN involved in the regulation of RSNA in rats with HF. Exercise training significantly restored the decreased number of neuronal nitric oxide synthase (nNOS) positive neurons in the PVN (129±17 vs 99±6) in HF rats. nNOS mRNA expression and protein levels in the PVN were also significantly increased in HF-ExT rats compared to HF-sedentary rats. To examine the functional role of NO within the PVN, an inhibitor of NO synthase, L-NMMA was microinjected into the PVN. Dose-dependent increases in RSNA, arterial blood pressure (BP) and heart rate (HR) were produced in all rats. There was a blunted increase in these parameters in HF rats compared to the sham-operated rats. Exercise training significantly augmented RSNA responses in rats with HF (33% vs 20% at the highest dose) thus normalizing the responses. The NO donor, sodium nitroprusside (SNP), microinjected into the PVN, produced dose-dependent decreases in RSNA, BP and HR in both sham and HF rats. Exercise training significantly improved the blunted decrease in RSNA in HF rats (36% vs 17% at the highest dose). In conclusion, our data indicates that ExT improves the altered NO mechanism within the PVN and restores NO mediated changes in RSNA in rats with HF.




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