Combined effects of phenoxybenzamine and propranolol in hypertensive rats

A hypothesis that the beta-adrenergic blocking drugs may possess weak alpha-adrenergic blocking activity, and that their antihypertensive effect may be due to this combined alpha - and beta-adrenergic blockade was tested. Phenoxybenzamine (PBZ) and propranolol (PPL) were selected as alpha - and beta-blocking drugs, respectively. They were given orally at doses of 1--100 mg/kg per day, 5 days per week. Their combined antihypertensive effects were determined in spontaneously hypertensive; deoxycorticosterone and salt hypertensive; and two kidney, one clip renal hypertensive rats. PBZ treatment showed antihypertensive effect in three models of hypertensive rats. However, addition of PPL either did not affect or rather antagonized the effect of PBZ. Moreover, the combined treatment increased side-effects, typically seen as urinary incontinence. The results did not support the above hypothesis, at least when the blockade was caused with PBZ and PPL.