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Am J Physiol Regul Integr Comp Physiol 267: R635-R644, 1994;
0363-6119/94 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 267, Issue 3 635-R644, Copyright © 1994 by American Physiological Society

ARTICLES

Phosphoinositide turnover signaling stimulated by ET-3 in endothelial cells from spontaneously hypertensive rats

K. Yokokawa, J. Johnson, M. Kohno, A. K. Mandal, M. Yanagisawa, T. Horio, K. Yasunari and T. Takeda
First Department of Internal Medicine, Osaka City University Medical School, Japan.

Endothelin (ET) B-type receptor-mediated signal transduction after stimulation with ET-3 was examined in cultured aortic endothelial cells obtained from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. The purpose of this study was to elucidate ETB receptor-mediated response in endothelial cells from hypertensive rat models. Non-isopeptide-selective displacement and affinity in these binding experiments suggest that aortic endothelial cell receptors for ET-3 correspond to ETB receptor subtypes. These receptors for ET-3 were similar in WKY and SHR endothelial cells. ETB receptor mRNA expression in cultured endothelial cells was also similar in WKY and SHR. However, the cytosolic free Ca2+ level in the absence of extracellular Ca2+ as well as the inositol 1,4,5-trisphosphate level in response to ET-3 were greater in endothelial cells from SHR than in those from WKY. Phospholipase C and protein kinase C activities after stimulation with ET-3 were also greater in SHR than in WKY. The 6-ketoprostaglandin F1 alpha production was also augmented in SHR, although nitric oxide formation and guanosine 3',5'-cyclic monophosphate production after stimulation with ET-3 were similar in WKY and SHR. We conclude that the phosphoinositide turnover signaling stimulated by ET-3 is augmented in cultured aortic endothelial cells from SHR compared with those from WKY.


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