Peptidergic Induction of Endothelin 1 and Prostanoid Secretion in Human Cerebromicrovascular Endothelium

Abstract

Angiotensin (Ang II) and arginine vasopressin (AVP), known vasoconstrictive agents, have been implicated as playing a role in the pathogenesis of hypertension. These peptides are among a number of neurotransmitters, hormones or cytokines that have been shown to induce endothelin 1 (ET-1) (a potent vasoconstrictor) or prostaglandins, in a variety of cellular systems including endothelium (1-4). None of the previous investigations, using either in vitro or in vivo model systems, have demonstrated a concomitant Ang II- or AVP-stimulated production of ET-1 and prostanoids. Since vascular diseases such as hypertension and vasospasm may be the result of an altered vascular balance between vasodepressors [vasodilatory peptides, prostanoids, endothelial-derived relaxing factor (EDRF)] and vasopressors [vasoconstrictive peptides, prostanoids, endothelial-derived constrictive factor (EDCF)] produced by the endothelium (5-8), we studied the type and possible mechanism of some mediators simultaneously elicited by AVP or Ang II in endothelium derived from capillary and microvessels of human brain (HBEC). This report describes an interrelationship between AVP- and Ang II-induced formation of ET-1 and prostanoids which can be modulated by either inhibitors of phospholipase A₂ (PLA₂), cyclooxygenase, or lipoxygenase.