Antihypertensive effect of combined treatment with alpha- and beta-adrenergic blockers in the spontaneously hypertensive rat.

Using a continuous systolic monitor, effects of oral administration of three alpha-adrenergic blockers, i.e. phenoxybenzamine, phentolamine and a new quinazoline compound (2-[4-(n-butyryl)-homopiperazine-1-yl]-4-amino-6, 7-dimethoxy-quinazoline; E-643), on blood pressure and heart rate in normotensive Wistar rats (NWR) and spontaneously hypertensive rats (SHR). 1) An oral dose of 1 mg/kg phenoxybenzamine or E-643 almost completely reversed pressor response to adrenaline (2 microgram/kg i.v). Phentolamine was 3 to 5 times less effective than phenoxybenzamine and E-643. These alpha-blockers reduced pressor response to noradrenaline (2 microgram/kg i.v.) merely to one half at an oral dose of 100 mg/kg. 2) All these alpha-blockers did not reduce blood pressure but markedly increased heart rate in NWR. On the other hand, they reduced blood pressure of SHR without marked increase in heart rate. Although the alpha-blocking and cardiac stimulating effects of phenoxybenzamine lasted more than several days, its hypotensive effect in SHR disappeared within 24 hours. 3) An oral dose of 30 mg/kg propranolol did not reduce blood pressure in both NWR and SHR but slightly decreased heart rate. The combined treatment of these alpha-blockers with propranolol completely abolished the cardiac stimulating effect of the alpha-blockers and resulted in a definite reduction in blood pressure of NWR and potentiated the hypotensive effect of alpha-blockers in SHR.