Differential Role of Neurohypophysial Hormones in Hypotension and Nitric Oxide Production During Endotoxaemia.

Abstract

Besides their well-established endocrine roles, vasopressin and oxytocin are also important regulators of immune function, participating in a complex neuroendocrine-immune network. In the present study, we investigated whether and how vasopressin and oxytocin could modulate lipopolysaccharide (LPS)-induced nitric oxide (NO) production in a well-established model of experimental endotoxaemia. Male Wistar rats were previously treated i.v. with vasopressin V1 or oxytocin receptor antagonists and then received either an i.v. LPS injection to induce endotoxaemia or a saline imjection as a control. The animals were divided into two groups: in the first group, blood was collected at 2, 4 and 6h after LPS injection; in the second group, mean arterial blood pressure (MABP) and heart rate (HR) were recorded over 6h. Plasma vasopressin and oxytocin values were higher in LPS- compared to saline-injected animals at 2 and 4h but returned to basal levels at 6h. NO levels exhibited an opposite pattern, showing a progressive increase over the entire period. The previous administration of a vasopressin V1 receptor antagonist significantly reduced NO plasma concentrations at 2 and 4h but not at 6h. By contrast, oxytocin receptor agonist pre-treatment had no effect on the NO plasma concentration. In relation to MABP, previous treatment with vasopressin V1 receptor antagonist reversed the LPS-induced hypotension at 4h, although this was not the case for oxytocin antagonist-treated animals. None of the antagonists affected HR. Our findings indicate that vasopressin (but not oxytocin) has effects on NO production during endotoxaemia in rats, although they do not lend support to the proposed anti-inflammatory actions of vasopressin during endotoxaemia.