AJP - Cell Physiology, Vol 266, Issue 3 C654-C660, Copyright © 1994 by American Physiological Society

ARTICLES

Vasoconstrictive peptides induce endothelin-1 and prostanoids in human cerebromicrovascular endothelium

M. Spatz, D. Stanimirovic, F. Bacic, S. Uematsu and R. M. McCarron
Stroke Branch, National Institute of Neurological Disorders and Stroke, Bethesda 20892.

Vasoconstrictive peptides and prostanoids have been implicated in the pathogenesis of hypertension and vasospasm. Recently, we have shown that human cerebromicrovascular endothelium [human brain endothelial cells (HBEC)] constitutively produces both endothelin-1 (ET-1) and prostanoids. The vasoactive peptides, arginine vasopressin (AVP) or angiotensin II (ANG II), stimulated secretion of both immunoreactive ET-1 and prostanoids from HBEC by a receptor-mediated induction of phospholipase C (PLC) and PLA2. The release of constitutive or AVP- or ANG II-induced ET-1 occurred at different rates during the 24-h incubation of HBEC in serum-free medium. The temporal profile of AVP-stimulated production of prostanoids differed from that of ANG II. AVP-induced release of prostaglandin D2 (PGD2) persisted for 24 h, whereas ANG II-stimulated PGD2 was only seen during the first 4 h of incubation. ANG II maximally stimulated PGI2 secretion during the 4- to 8-h interval, whereas AVP did not stimulate PGI2 secretion. Dexamethasone (Dxm), indomethacin (Indo), and nordihydroguaiaretic acid, the respective inhibitors of PLA2-cyclooxygenase II, cyclooxygenase, and lipoxygenase, increased both constitutive and AVP- or ANG II-stimulated secretion of ET-1. Dxm also decreased AVP- or ANG II-stimulated production of PGD2 and PGF2 alpha. These results indicate an interrelationship between HBEC production of ET-1 and prostanoids, which may play a role in regulating cerebral microcirculation.

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