Central and systemic effects of a vasopressin V1 antagonist on MAP recovery after haemorrhage in rats.

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 animals were killed and selected brain regions and plasma taken for AVP measurement. Intravenous (i.v.) administration of d(CH2)5Tyr(Me)AVP at 10 micrograms kg-1, but not 100 ng kg-1, significantly reduced MAP between 20 and 45 min posthaemorrhage compared with saline-treated controls. In contrast, administration of d(CH2)5Tyr(Me)AVP at 100 ng kg-1 intracerebroventricularly caused an attenuated MAP recovery to haemorrhage comparable with the effect of the antagonist at 10 micrograms 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 micrograms 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.