Tolerance to haemorrhage during vasopressin antagonism and/or captopril treatment in conscious sheep

Abstract

The effect of separate and combined blockade of vasopressin (AVP) V1-receptors and angiotensin II formation on resistance to a slow venous haemorrhage (0.7 ml kg-1 min-1) was studied in six conscious adult sheep by bleeding to the point of an abrupt fall in the mean systemic arterial pressure (MSAP). Intravenous administration of the V1-receptor antagonist [d(CH2)5Tyr(Me)AVP] (10 micrograms kg-1) and/or the angiotensin I converting enzyme inhibitor captopril (20 mg + 1 mg h-1) did not cause any significant haemodynamic changes in the normovolaemic animal. The volume of haemorrhage necessary to induce acute hypotension (MSAP < 50 mmHg) was significantly smaller after AVP blockade alone (13.8 +/- 0.7 ml kg-1; P < 0.01) but not after captopril treatment (14.7 +/- 1.6 ml kg-1; n.s.) compared to control animals receiving no drug treatment (16.8 +/- 0.6 ml kg-1). The combined treatment with the AVP antagonist and captopril caused a further decrease in tolerance to haemorrhage (9.4 +/- 1.2 ml kg-1; P < 0.001). Blockade of AVP V1-receptors was associated with an attenuated increase in systemic vascular resistance immediately after the end of haemorrhage, concomitant with an accentuated lowering of the central venous pressure. In contrast, captopril treatment decreased the degree of vasoconstriction mainly during the second half of the posthaemorrhage observation period of 1 hour. It is concluded that both AVP and angiotensin II contribute to the maintenance of the MSAP during haemorrhage in conscious sheep.(ABSTRACT TRUNCATED AT 250 WORDS)