Differential vasorelaxant effects of milrinone and amrinone on contractile responses of canine coronary, cerebral, and renal arteries.
The vasorelaxant effects of milrinone and amrinone in canine coronary, cerebral, and renal arterial rings or strips contracted by either K+-depolarization, U46619 (a thromboxane mimetic), or prostaglandin F2 alpha (PGF 2 alpha) were quantitated. Milrinone was more potent as a vasorelaxant in coronary arteries relative to cerebral or renal arteries regardless of the mode of contraction; amrinone was coronary selective with K+ contraction only. When comparing potency in arteries contracted by different agonists, milrinone was significantly more potent as a vasorelaxant in all three arteries contracted by either U46619 or PGF2 alpha than in arteries contracted by K+ depolarization, whereas amrinone was only selective for U46619-induced contractions in cerebral arteries. This profile of activity for milrinone was similar to that of sodium nitrite and isoproterenol and dissimilar from the calcium entry blocking agents nimodipine and nifedipine. In conclusion, this study shows that coronary vascular selectivity exists for milrinone and amrinone. Moreover, the relaxant profiles of milrinone and amrinone, with different sources of vascular smooth muscle, are unlike those of calcium entry blocking agents and more similar to the profiles of agents that modulate cyclic nucleotide levels.
Harris
A L
AL
Department of Pharmacology, Sterling-Winthrop Research Institute, Rensselaer, New York 12144.
Grant
A M
AM
Silver
P J
PJ
Evans
D B
DB
Alousi
A A
AA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000676:Amrinone / Q000494:pharmacology*; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D020105:Milrinone; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009553:Nimodipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology*; D012077:Renal Artery / Q000187:drug effects; D012977:Sodium Nitrite / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D011728:Pyridones; D009553:Nimodipine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; D020105:Milrinone; D000676:Amrinone; D007545:Isoproterenol; D012977:Sodium Nitrite; D011188:Potassium