Effects of prolonged administration of indenolol in hypertensive rats

The effects of 4-week administration and subsequent 2-week withdrawal of indenolol, 50 mg/kg/day p.o., were investigated in spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR) and DOCA-salt hypertensive rats (DHR) at established stage, and compared with those of propranolol, 100 mg/kg/day p.o. Indenolol and propranolol caused a marked decrease in heart rate in SHR, RHR and DHR without showing a pronounced antihypertensive activity. Both drugs did not affect the body weight gain in RHR and DHR. On the other hand, the drugs suppressed the body weight gain in SHR, which recovered during 2-week withdrawal period. Weights of the heart, kidney, liver, spleen and adrenals were not affected by the drugs. Indenolol and propranolol markedly lowered the plasma renin activity (PRA) in SHR, RHR and DHR. PRA in RHR and DHR recovered to the control level during 2-week withdrawal period, while that in SHR did not. The results indicate that indenolol produces essentially the same effect as propranolol in SHR, RHR and DHR. Prolonged administration of indenolol to SHR, RHR and DHR with established hypertension produces a marked suppression of cardiac performance and PRA with showing antihypertensive activity.