Analysis of hypotensive mechanisms of pindolol, a beta-adrenoceptor blocking drugs in rats.

The hypotensive mechanisms of pindolol in anesthetized and conscious rats were investigated. Pindolol caused a fall in blood pressure in anesthetized, conscious and spinal rats, though in conscious rats a higher dose of the drug was required to produce such a response. This hypotension with pindolol in anesthetized and conscious rats was markedly inhibited by pretreatment with the drug itself or other beta-adrenoceptor blocking drugs. A similar phenomenon also occurred when isoproterenol was injected intravenously in anesthetized and conscious rats. The relationship between the hypotensive actions of four beta-adrenoceptor blocking drugs in anesthetized rats and their intrinsic beta-sympathomimetic actions in isolated catecholamine-depleted tracheal preparations was determined. Order of hypotensive potencies was the same as that of their intrinsic beta-sympathomimetic action, namely, pindolol greater than carteolol greater than bufetolol in equilibrium propranolol (p less than 0.05). These results suggest that the hypotension with pindolol is mediated through a decrease in the peripheral vascular resistance due to an intrinsic beta-sympathomimetic action of the drug.