Selective V1a receptor agonist FE 202158 reverses platelet-activating factor-induced hypotension, vascular leak, impaired tissue perfusion, and mortality in rats

Abstract

Platelet-activating factor (PAF) is a phospholipid autacoid inducing peripheral vasodilation and vascular leak, both pathophysiological hallmarks of sepsis-induced cardiovascular dysfunction resulting in hypotension [1]. Indeed, PAF has been implicated in various animal models of sepsis and in septic humans [2]. A deficiency in the vasopressor hormone arginine vasopressin (AVP), a mixed V1a/V2 receptor agonist, also contributes to the cardiovascular dysfunction of septic shock, leading to clinical use of AVP for this condition [3,4]. These various findings led us to hypothesize that the selective V1a receptor agonist FE 202158 would be effective in a rat model of PAF-induced hypotension.