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)

Effects of losartan, prazosin and a vasopressin V1‐receptor antagonist on renal and femoral blood flow in conscious sheep

“…The absence of haemodynamic effects, including regional blood flow, after blockade of AVP V 1 ‐receptors is in agreement with numerous observations in several mammalian species (Share 1988, Ullman et al . 1992b).…”

“…The Na intake was not controlled in this study. The PRA levels observed were very low, being about one order of magnitude lower than that seen in Na replete sheep (daily Na intake: 70 mmol) (Ullman et al . 1992b), indicating a high voluntary intake of Na.…”

“…In previous studies we have observed signs of compensatory ability between the AVP and angiotensin systems on systemic blood pressure and flow during general anaesthesia and hypotensive haemorrhage, respectively (Ullman et al . 1992a, b). The AVP‐a and PRAZ were without significant effect on RBF, indicating that AVP or adrenergic influences appear to be minor determinants of this variable in conscious individuals.…”

“…We have previously studied the effects of pharmacological blockade of ANG II formation and AVP V 1 receptors on blood pressure and central haemodynamics in anaesthetized non‐stressed sheep (Ullman et al . 1992a) and cardiovascular responses to haemorrhage in conscious animals (Ullman et al . 1992b).…”

“…However, the possible role of basal circulating levels of angiotensin II (ANG II) and AVP for cardiovascular function, including regional blood¯ow, is not clear. We have previously studied the effects of pharmacological blockade of ANG II formation and AVP V 1 receptors on blood pressure and central haemodynamics in anaesthetized non-stressed sheep (Ullman et al 1992a) and cardiovascular responses to haemorrhage in conscious animals (Ullman et al 1992b). Redundancy of control mechanisms in cardiovascular control was apparent in those studies, based on the observation that either blockade had no or modest effects on arterial pressure and/or cardiac output, whereas marked responses were seen after the combination.…”