Central and Systemic Effects of a Vasopressin V1 Antagonist on MAP Recovery After Haemorrhage in Rats

Abstract

The present study examined the effects of central and peripheral administration of a vascular (V¹) vasopressin (AVP) receptor antagonist on blood pressure, heart rate, and AVP levels in conscious rats. Rats subjected to rapid arterial haemorrhage were administered the AVP V₁ antagonist [d(CH₂)₅Tyr(Me)AVP] either 5 min pre- or 20 min posthaemorrhage. Mean arterial blood pressure (MAP) was monitored for 45 min, after which the animais were killed and selected brain regions and plasma taken for AVP measurement. Intravenous (i.v.) administration of d(CH₂)₅Tyr(Me)AVP at 10 μg kg⁻¹, but not 100 ng kg⁻¹, significantly reduced MAP between 20 and 45 min posthaemorrhage compared with salinetreated controls. In contrast, administration of d(CH₂)₅Tyr(Me)AVP at 100 ng kg⁻¹ intracerebroventricu-larly caused an attenuated MAP recovery to haemorrhage comparable with the effect of the antagonist at 10 μg kg⁻¹ i.v. Haemorrhage caused a marked increase in circulating AVP levels, which was further enhanced in rats treated with the V₁ antagonist at 10 μg kg⁻¹ i.v., but no change in AVP levels of selected brain regions. The results indicate a role for AVP in MAP recovery following haemorrhage which may be centrally mediated.