Blunted nitric oxide-mediated inhibition of renal nerve discharge within PVN of rats with heart failure.
We have demonstrated a decreased neuronal nitric oxide (NO) synthase (nNOS) message in the hypothalamus of rats with heart failure (HF). Subsequently, we have demonstrated that NADPH diaphorase (a commonly used marker for nNOS activity) positive neurons are decreased in paraventricular nucleus (PVN) of rats with coronary artery ligation model of HF. The goal of the present study was to examine the influence of endogenous NO within the PVN on renal sympathetic nerve discharge (RSND) during HF. In alpha-chloralose- and urethane-anesthetized rats, an inhibitor of NO synthase, N(G)-monomethyl-L-arginine (L-NMMA) microinjected into the PVN (50, 100, and 200 pmol in 50-200 nl) produced a dose-dependent increase in RSND, blood pressure, and heart rate in control and HF rats. These responses were attenuated in rats with HF compared with control rats. On the other hand, the NO agonist, sodium nitroprusside, microinjected in PVN produced a dose-dependent decrease in RSND and blood pressure in control and HF rats. These responses were less in rats with HF compared with control rats. These data suggest that the endogenous NO-mediated effect within the PVN of HF rats is less potent in suppressing RSND compared with control rats. These data support the conclusion that the NO system within the PVN involved in controlling autonomic outflow is altered during HF and may contribute to the elevated levels of renal sympathoexcitation commonly observed in HF.
Zhang
K
K
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, Nebraska 68198-4575, USA.
Li
Y F
YF
Patel
K P
KP
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000294:innervation; D008026:Ligation; D008297:Male; D008845:Microinjections; D009433:Neural Inhibition / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000008:administration & dosage; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D004791:Enzyme Inhibitors; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase