RHO kinase and endothelium-dependent contractions in the SHR and WKY aorta

Abstract

The release of endothelium-dependent contracting factor (EDCF) isaugmented in the aorta of the spontaneously hypertensive (SHR)compared to that of the Wistar Kyoto (WKY) rats. EDCF eventuallyactivates TP receptors of the vascular smooth muscle cells. The presentstudy was designed to investigate the role of Rho kinase in EDCF-mediated responses. Quiescent aortic rings with endothelium of SHRand WKY were contracted with acetylcholine or the calcium ionophoreA23187 in the presence of L-NAME, isometric tension was measured.Two chemically distinct Rho kinase inhibitors, Y27632 and HA1077,reduced the contractions to both agonists, suggesting the importance ofRho kinase in EDCF-mediated responses. To study the role of Rhokinase in vascular smooth muscle cells, contractions to the TP receptoragonist U46619 or prostaglandin F2awere obtained in rings withoutendothelium of SHR and WKY aorta. The concentration response curveswere comparable in the two strains. The Rho kinase inhibitors Y27632and HA1077 inhibited the contractions to both U46619 and prostaglan-din F2a, but to a lesser extent than the endothelium-dependentcontractions to acetylcholine and A23187. These results suggest thatRho kinase is involved both in the release and the action of EDCF.