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In order to examine clinical potential for ecarazine, prazosin, phentolamine and hexamethonium to cause orthostatic hypotension in man, the effects of these drugs on the vasopressor reflexes induced by bilateral carotid artery occlusion (BCO) or head-up tilting (Tilt) have been investigated in gallamine-immobilized cats. Ecarazine at doses of 0.1 to 10 mg/kg i.v. decreased blood pressure in a dose-dependent way whereas at 0.1 to 1 mg/kg it did not affect the pressor response to BCO or Tilt and at 10 mg/kg it suppressed only the response to BCO slightly. On the other hand, prazosin, phentolamine and hexamethonium, at hypotensive doses, not only decreased blood pressure but also inhibited pressor responses to both BCO and Tilt. Because ecarazine lacks in producing orthostatic hypotension, it seems likely that the clinical propensity of drugs to cause such side effect is correlated with the inhibition of Tilt response rather than with that to BCO. The results of comparison of the inhibition by these drugs of Tilt response indicate that ecarazine is the most favorable drug among these four drugs and that phentolamine has the highest incidence of orthostatic hypotension. With respect to the effects of prazosin, phentolamine and hexamethonium, statistically significant correlation between the inhibition of the response to BCO and that to the compensatory reflex to Tilt has been observed. Hence it is suggested that the agents which decrease blood pressure by affecting peripheral sympathetic mechanisms might depress each efferent sympathetic pathway to the same degree.

journal of pharmacobio-dynamics

Effects of ecarazine, prazosin, phentolamine and hexamethonium on the vasopressor reflexes induced by bilateral carotid artery occlusion and head-up tilting in cats.