Enhanced phosphoinositide turnover signalling stimulated by endothelin B-type receptor in endothelial cells from spontaneously hypertensive rats

Abstract

1. Endothelin (ET) B-type (ETB) receptor-mediated signal transduction was examined after stimulation with ET-3 in cultured aortic endothelial cells (EC) from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats (8 weeks old). 2. The EC from both rat strains expressed only ETB receptor mRNA. The receptor densities and affinities, which were non-selective for ET-1, -2, -3 and Sarafotoxin S6c, and mRNA expression were similar in WKY and SHR. 3. The cytosolic Ca2+ level in the absence of extracellular Ca2+, inositol 1,4,5-trisphosphate levels, protein kinase C and phospholipase C activities in response to ET-3 were greater in SHR EC than in WKY EC. 4. The 45Ca uptake in response to ET-3, which was blocked by Ni2+, was smaller in SHR EC than in WKY EC. 5. The 6-keto-PGF1alpha production was augmented in SHR, though nitric oxide formation after stimulation with ET-3 was similar. 6. These results suggest that ETB receptor-mediated phosphoinositide turnover signalling is augmented in SHR EC through postreceptor mechanism.