VASOACTIVE AND BETA-ADRENOCEPTOR BLOCKING PROPERTIES OF 3,4-DIHYDRO-8-(2-HYDROXY-3-ISOPROPYLAMINO) PROPOXY-3-NITROXY-2H-1-BENZOPYRAN (K-351), A NEW ANTIHYPERTENSIVE AGENT

  • 1 January 1983
    • journal article
    • research article
    • Vol. 262  (1) , 132-149
Abstract
Single oral administration of K-351 showed a long lasting antihypertensive action in spontaneously hypertensive rats, accompanied by slight bradycardia. K-351 reduced systolic and diastolic blood pressures almost to the same degree. K-351 showed a competitive antagonistic effect on norepinephrine-induced contraction of isolated canine blood vessels. This .alpha.-adrenoceptor blocking action of K-351 was about 5 times less potent than that of phentolamine. K-351 produced a nitroglycerin-like relaxant action on isolated blood vessels previously contracted with high K+. K-351 showed a nonselective .beta.-adrenoceptor blocking action in isolated guinea pig atrium and trachea, and its action was about 2 times more potent than that of propranolol. K-351 did not show an intrinsic sympathomimetic action. In anesthetized dogs, low doses of K-351 reduced the heart rate and antagonized the positive chronotropic and hypotensive responses to isoproterenol. In higher doses, K-351 lowered the blood pressure and showed an antagonistic action on the pressor response to phenylephrine. The desnitro compound of K-351 was deprived of vasoactive properties on isolated blood vessels and hypotensive activity. K-351 evidently has both .beta.-adrenoceptor blocking and vasoactive properties which may result in an antihypertensive effect without reflex tachycardia in hypertensive animals.