Investigations on the Antihypertensive Activity of Timolol and Bendroflumethiazide and the Combination in Dogs and Rats

Abstract

The effects of timolol and bendroflumethiazide, either alone or combined in a fixed ratio of 4:1, on blood pressure, plasma renin activity, and plasma potassium concentration, have been investigated in normotensive and renal hypertensive dogs, and in normotensive and spontaneously hypertensive rats. In addition, the urinary kallikrein excretion has been measured in normotensive and hypertensive rats. When administered to hypertensive dogs and rats, the drug combination significantly reduced the blood pressure. Marginal reductions were observed in normotensive animals or after the administration of the single drugs. The thiazide–induced hypokalemia and hyperreninaemia were almost completely antagonised by the concomitant administration of timolol in both animal species. A highly significant elevation of urinary kallikrein excretion was also observed in rats treated with the drug combination. A less marked increase of kallikrein excretion was noted in the bendroflumethiazide treated rats. The possibility that renal haemodynamic changes, in addition to the inhibition of the increase in plasma renin, play a role in the observed antihypertensive effects is discussed.

Effects on Rat Urinary Kallikrein Excretion of Bumetanide, Bendroflumethiazide and Hydralazine

“…We have recently observed however an enhancement of urinary kallikrein excretion when the hyperreninemia induced by bendroflumethiazide was suppressed by concomitant administration of the p-blocking agent timolol (KERGAARD NIELSEN et al 1976). In addition an enhancement of the antihypertensive effect of bendroflumethiazide was observed.…”