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.
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. Furthermore, 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 anesthethized 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. Results have revealed that K-351 has both beta-adrenoceptor blocking and vasoactive properties which may result in an antihypertensive effect without reflex tachycardia in hypertensive animals.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D011412:Propanolamines; D014665:Vasodilator Agents; C036089:nipradilol; D011188:Potassium; D009638:Norepinephrine