Role of the alpha-adrenergic blocking effect in the acute hypotensive effect of beta-adrenergic blocking drugs with alpha-blocking activities in conscious SHR.

Acute hypotensive effects and the mechanisms of three beta-adrenergic blocking drugs with alpha-blocking activity were studied in comparison with those of prazosin, propranolol and hydralazine in the conscious spontaneously hypertensive rat (SHR). Prazosin lowered the blood pressure dose-dependently and inhibited the pressor response to phenylephrine. Three beta-adrenergic blocking drugs with alpha-blocking activity, labetalol (30 mg/kg), arotinolol (100 mg/kg) and nipradilol (100 mg/kg) also lowered the blood pressure to the same extent as prazosin (0.3 mg/kg), but the inhibition of the pressor response to phenylephrine produced by them was disproportionately slight. Propranolol (100 mg/kg) did not lower the blood pressure. These results suggest that the acute hypotensive effects of three beta-adrenergic blocking drugs with alpha-blocking activity were attributable only partially to the alpha-adrenergic blocking effect; a mechanism or mechanisms other than the alpha-adrenergic blocking effect must be invoked to explain the acute hypotensive effect produced by lower doses of these drugs in the conscious SHR.