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

The regulation of blood flow to different organs is determined by the autonomic nervous system and systemic and/or local vasoactive substances. Although the cardiovascular effects of the renin-angiotensin system (RAS), the sympathoadrenal system and vasopressin (AVP) have been thoroughly studied, there are relatively few investigations on these systems with concomitant measurements of systemic haemodynamics and regional blood flow in conscious unstressed individuals. We therefore studied effects of pharmacological blockade of AVP V1-, angiotensin II (ANG II) AT1-and adrenergic alpha-receptors on central and regional (renal and femoral blood flow) haemodynamics in adult conscious ewes. Eight adult cross-bred ewes were chronically intrumented with peri-vascular ultrasonic flow probes implanted unilaterally around the renal and the femoral artery. While standing in their habitual environment, systemic and regional haemodynamics were measured before and after the following treatments as single intravenous injections. Animals in group A (n = 6) were given isotonic saline (NaCl) followed by the AT1-receptor blocker losartan (LOS, 10 mg kg-1) 30 min later; group B (n = 6) animals were given the alpha-adrenoceptor blocker prazosin (PRAZ, 0.2 mg kg-1); and group C (n = 6) the vasopressin V1 receptor antagonist [d(CH2)5Tyr(Me)AVP] (AVP-a, 10 microg kg-1). PRAZ reduced mean arterial pressure (MAP) by 11% concomitant with an increase in heart rate (HR) (32%), whereas the other substances where without effect on those variables. Femoral blood flow (FBF) was enhanced (increased by 82%) by injection of PRAZ only. Administration of LOS increased the renal blood flow (RBF) by 11% while the other drugs were without effect on that parameter. We conclude that basal renal vascular tone in conscious unstressed sheep is dependent on angiotensinergic mechanism and that blockade of this influence causes a local increase in flow without concomitant effects on systemic haemodynamics.