Antihypertensive Effect of Combined Treatment with α- and β-Adrenergic Blockers in the Spontaneously Hypertensive Rat

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Using a continuous systolic monitor, effects of oral administration of three α-adrenergic blockers, i.e. phenoxybenzamine, phentolamine and a new quinazoline compound (2-[4-(n-butyryl)-homopiperazine-1-yl]-4-amino-6, 7-dimenthoxy-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 μg/kg i.v.). Phentolamine was 3 to 5 times less effective than phenoxybenzamine and E-643. These α-blockers reduced pressor response to adrenaline (2 μg/kg i.v.) merely to one half at an oral dose of 100 mg/kg. 2) All these α-blockers did not other hand, they reduced blood pressure of SHR without marked increase in heart rate. Although the α-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 α-blockers with propranolol completely abolished the cardiac stimulating effect of the α-blockers and resulted in a difinite reduction in blood pressure of NWR and potentiated the hypotensive effect of α-blockers in SHR.
社団法人日本循環器学会の論文
1977-09-20