Effects of azimilide on cardiovascular tissues from normo- and hypertensive rats.
We tested whether azimilide has potential for use in the treatment of heart failure. Azimilide, > or =3 x 10(-5) M, had no effect on the quiescent Wistar-Kyoto (WKY) rat aorta, or mesenteric and intralobar pulmonary arteries. Azimilide > or =3 x 10(-5) M relaxed the KCl-contracted aorta and portal vein. Azimilide, 10(-7)-10(-5) M, prolonged the WKY left ventricular action potential and augmented the force of contraction of left ventricle strips from 12- and 22-month-old WKY rats. Spontaneously hypertensive rats (SHRs), at ages 12 and 22 months, are models of cardiac hypertrophy and failure, respectively. The augmentation of force with azimilide was similar on 12- and 22-month-old WKY rats and 12-month-old SHRs but reduced on the 22-month-old SHR left ventricle. Azimilide, 3 x 10(-6) and 10(-5) M, augmented the force responses of the 22-month-old SHR left ventricle by 40 and 50%, respectively. As azimilide is a vasodilator and positive inotrope in the rat, and the positive inotropic effect is present in heart failure, azimilide should undergo further testing as a positive inotrope for the treatment of heart failure.
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Cardiovascular Pharmacology Group, Faculty of Medicine and Health Science, The University of Auckland, New Zealand.
Doggrell
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SA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects*; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D006827:Hydantoins; D006973:Hypertension / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011169:Portal Vein / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D002316:Cardiotonic Agents; D006827:Hydantoins; D007093:Imidazoles; D048289:Imidazolidines; D010879:Piperazines; C086123:azimilide