Endothelin in the Central Nervous System and Regulation of Vasopressin 
Secretion and Arterial Pressure

The integration of arterial pressure and volume regulation is vital for hemodynamic stability. The sympathetic nervous system plays a key role in the acute regulation of arterial pressure. Under chronic physiologic conditions or pathophysiological states, such a heart failure, the baroreflex adapts to arterial pressure. This adaptation argues against an exclusive role for long-term baroreflex control of arterial pressure. Rather, chronic regulation of systemic hemodynamics requires neural and hormonal factors that modulate the baroreflex and sympathetic efferent activity. In addition to their peripheral actions, two potent neurohumoral factors, endothelin and vasopressin act at selected central nervous system sites and play a vital role in this regulation. Work from our laboratory and that of others has shown that ET and AVP work in an integrated manner that permits a robust and concerted action to regulate both volume and pressure. Our long term objective is to ascertain the mechanisms whereby the endothelin-vasopressin-sympathetic system regulates hemodynamics during heart failure and hypertension, with a view to identifying new areas to target for therapy. 

      Our laboratory is currently working on the identification of the mediators and modulators of endothelin-induced vasopressin release and pressor activity at selected hypothalamic sites by using a combination of in vitro and in vivo techniques. We hypothesized that ET differentially regulates vasopressin and arterial pressure at distinct hypothalamic loci via glutamatergic, GABAergic and purinergic mechanisms under normal, heart failure, and hypertensive conditions

This page was created and maintained by Christine Cupps
updated: 09/15/2004