Cardiovascular effects of prazosin in dogs

1. In pentobarbitone-anaesthetized dogs, prazosin (2 x 1-3 micronmol day-1 kg-1; 2 x 0-5 mg day-1 kg-1) administered orally for 3 days reduced resting aortic blood pressure as well as the pressor response to bilateral carotid occlusion. Prazosin neither affected resting heart rate nor the tachycardia induced by intravenous isoprenaline, noradrenaline and electrical stimulation of preganglionic and postganglionic sympathetic nerve fibres. Prazosin significantly attenuated the fall in perfusion pressure in a perfused hind leg resulting from the section of the ipsilateral sympathetic lumbar chain. Furthermore, the drug inhibited by about 50% the hind-leg pressor responses elicited by intra-arterial administration of alpha-adrenoreceptor agonists and by stimulation of the lumbar sympathetic chain, without altering the effects of angiotension II. 2. Acute administration of prazosin into the innervated hind leg provoked a dose-related reduction in vascular resistance. However, after spinal anaesthesia no such an effect was observed even when vascular tone was increased by infusion of vasopressin. Under the same experimental conditions administration of papaverine induced a vasodilatation. 3. This study confirms that prazosin impairs the function of vascular alpha-adrenoreceptors, and strongly challenges the claim that this compound produces a directly mediated vasodilatation of the leg vascular bed.