Submitted on May 26, 2004
Accepted on November 23, 2005
ANGIOTENSIN-MEDIATED INCREASE IN RENAL SYMPATHETIC NERVE DISCHARGE WITHIN THE PVN: ROLE OF NITRIC OXIDE
Yi-Fan Li1, Wei Wang2, William G Mayhan2, and Kaushik P Patel2*
1 Division of Basic Biomedical Science, College of Medicine, University of South Dakota, Vermillion, SD, USA
2 Physiology and Biophysics, University of Nebraska Medical Center, Omaha, NE, USA
* To whom correspondence should be addressed. E-mail: kpatel{at}unmc.edu.
The paraventricular nucleus (PVN) of the hypothalamus is known as an important site of integration in the central nervous system for sympathetic outflow. Both angiotensin II (Ang II) and nitric oxide (NO) play an important role in the regulation of sympathetic nerve activity. The purpose of the present study was to examine the interaction between NO and Ang II within the PVN on 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 NG- monomethyl-L-arginine (L-NMMA) into the PVN. We found that 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, increasing 53±9%, 19±3 mmHg and 32±12 beats/min from the baselines respectively, at the highest dose. These responses were significantly enhanced by prior microinjection of L-NMMA and were blocked by losartan, an AT1 receptor antagonist. Similarly, administration of antisense to nNOS within the PVN also potentiated the Ang II responses. Conversely, overexpression of nNOS within the PVN with adenoviral gene transfer significantly attenuated Ang II responses. Furthermore, using the push-pull technique, admiistration of Ang II (1 nmol) into the PVN induced an increase in NO release. In conclusion, our data indicate that Ang II AT1 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.
