Angiotensin-mediated increase in renal sympathetic nerve discharge within the PVN: role of nitric oxide.
The paraventricular nucleus (PVN) of the hypothalamus is known to be an important site of integration in the central nervous system for sympathetic outflow. ANG II and nitric oxide (NO) play an important role in regulation of sympathetic nerve activity. The purpose of the present study was to examine how the interaction between NO and ANG II within the PVN affects sympathetic outflow in rats. Renal sympathetic nerve discharge (RSND), arterial blood pressure (AP), and heart rate (HR) were measured in response to administration of ANG II and N(G)-monomethyl-l-arginine (L-NMMA) into the PVN. Microinjection of ANG II (0.05, 0.5, and 1.0 nmol) into the PVN increased RSND, AP, and HR in a dose-dependent manner, resulting in increases of 53 +/- 9%, 19 +/- 3 mmHg, and 32 +/- 12 beats/min from baseline, respectively, at the highest dose. These responses were significantly enhanced by prior microinjection of L-NMMA and were blocked by losartan, an ANG II type 1 receptor antagonist. Similarly, administration of antisense to neuronal NO synthase within the PVN also potentiated the ANG II responses. Conversely, overexpression of neuronal NOS within the PVN with adenoviral gene transfer significantly attenuated ANG II responses. Push-pull administration of ANG II (1 nmol) into the PVN induced an increase in NO release. Our data indicate that ANG II type 1 receptors within the PVN mediate an excitatory effect on RSND, AP, and HR. NO in the PVN, which can be induced by ANG II stimulation, in turn inhibits the ANG II-mediated increase in sympathetic nerve activity. This negative-feedback mechanism within the PVN may play an important role in maintaining the overall balance and tone of sympathetic outflow.
Li
Yi-Fan
YF
Division of Basic Biomedical Science, College of Medicine, University of South Dakota, Vermillion, South Dakota, USA.
Wang
Wei
W
Mayhan
William G
WG
Patel
Kaushik P
KP
D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D025461:Feedback, Physiological; D006339:Heart Rate / Q000187:drug effects; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008845:Microinjections / Q000379:methods; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D000809:Angiotensins; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D019808:Losartan