Abstract 644: The Endothelin B Receptor Attenuates Endothelin Contraction Via An Endothelium Independent Mechanism In Mesenteric Arteries Of (mRen2)27 Rats
Endothelin-1 (ET-1) and Angiotensin II (Ang II) are important modulators of vascular tone. Contraction to ET-1 is dependent on the activation of ETA and ETB receptors. The contractile receptor ETA is localized in the smooth muscle cells whereas ETB receptors are predominantly found in the endothelium. We investigated the role of ETB receptors in ET-1 contraction in a model of Ang II-dependent hypertension, the (mRen2)27 rat. Third branch mesenteric arteries were isolated from 12 weeks old male Sprague-Dawley (SD) control and (mRen2)27 hypertensive rats and mounted on a wire Multi Myograph (Model 620, DMT) for determination of isometric force. Dose response curves to ET-1 (10-11-10-7M) were performed in arterial segments that were either intact, endothelium denuded or preincubated with the ETB specific antagonist BQ788 10-6M. Endothelial denudation was performed by passing a human hair through the arterial lumen and functional loss of the endothelium was confirmed by the absence of vasodilatation to acetylcholine. Maximal responses were expressed as percent of maximal response to 75mM KCl (%KMAX) and the sensitivity as pD2 (pD2= -Log[EC50]). In SD control rats, addition of BQ788 significantly increased ET-1 sensitivity in intact arteries (8.9±0.1 vs 9.3±0.1, p<0.05) and the increase was abolished by endothelial denudation with no change in maximal response. However, the ETB blocker BQ788 increased the maximal tension in both intact (127±2 vs 154±13 %KMAX, p<0.05); and denuded (156±9 vs 188±12 %KMAX, p<0.05) arteries from (mRen2)27 rats with no change in sensitivity. In summary, the present results demonstrate that endothelial ETB receptors influence vasodilatory function in control SD rats, but apparently attenuate the contraction to ET-1 in the (mRen2)27 rats. We conclude that the expression of ETB receptors in the endothelium and smooth muscle of resistance vessels in the (mRen2)27 rats may function as a compensatory mechanism to the increased blood pressure or activated angiotensin system found in this model of hypertension.
- © 2013 by American Heart Association, Inc.