Haemodynamic response to ketanserin in rabbits with Page hypertension: comparison with prazosin

The role of alpha 1-adrenoceptors in the hypotensive response to ketanserin was studied in conscious normotensive (sham-operated) and Page hypertensive (two-kidney, two wrapped) rabbits. Ketanserin (0.01, 0.1 and 1 mg/kg i.v.) was administered at 30 min intervals on four experimental days: no pretreatment; after prazosin 1 mg/kg and infusion; after pharmacological 'total' autonomic effector block (TAB) and with repeated three point methoxamine dose-response lines. Only the highest dose (1 mg/kg) of ketanserin lowered blood pressure and dilated the iliac vascular bed (Doppler flowmeter) in both wrap and sham-operated rabbits. Prazosin pretreatment and TAB prevented these effects. Ketanserin (1 mg/kg) also caused significant alpha 1-adrenoceptor antagonism as measured by a 2.5-fold shift in the methoxamine dose-response lines. In separate experiments prazosin (0.01-0.1 mg/kg i.v. bolus) caused similar falls in blood pressure and alpha 1-adrenoceptor block as ketanserin 0.3 and 1 mg/kg. The only difference observed between prazosin and ketanserin was the substantial reflex tachycardia to prazosin that was absent after ketanserin. These results suggest that in normotensive rabbits and in rabbits with Page hypertension the hypotensive response to ketanserin can be explained by alpha 1-adrenoceptor antagonism.