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Evaluation of a novel antihypertensive agent ly 127210 7 8 dimethoxy 1h 3 benzazepin 2 amine hydrochloride in anesthetized and conscious spontaneously hypertensive rats


Journal of Pharmacology & Experimental Therapeutics 232(1): 134-138
Evaluation of a novel antihypertensive agent ly 127210 7 8 dimethoxy 1h 3 benzazepin 2 amine hydrochloride in anesthetized and conscious spontaneously hypertensive rats
LY127210 is a novel peripheral arterial vasodilator that reduces mean arterial blood pressure in anesthetized and conscious spontaneously hypertensive rats by all conventional routes of administration. The antihypertensive activity of LY127210 results predominantly from a decrease in total peripheral vascular resistance, and to a degree of reflex tachycardia produced by LY127210 in conscious spontaneously hypertensive rats is significantly less than that produced by hydralazine at equivalent antihypertensive doses. The relative lack of reflex tachycardia produced by LY127210 appears to result from a direct bradycardic effect of the compounds that occurs at the level of the myocardium at doses similar to those required to produce peripheral arteriolar vasodilation. Apparently the direct bradycardic effect of LY127210 serves to offset, at least in part, the tachycardia resulting from reflex stimulation of sympathetic outflow that occurs on activation of the baroreflex loop as blood pressure is lowered. LY127210 may provide adequate control of blood pressure and may not require the concomitant administration of a .beta.-adenoceptor antagonist to control reflex tachycardia, as is commonly necessary with hydralazine.


Accession: 005395468



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