Propranolol antagonizes coronary artery relaxation by a potassium channel opener.
Coronary artery preparations from cattle hearts responded with stable contractions to the thromboxane A2 analogue, U 46619. These contractions were progressively reduced by increasing concentrations of the prototypical potassium channel opener pinacidil (3.8 x 10(-8) to 1.1 x 10(-4) M). Pinacidil-induced relaxations were antagonized significantly by d,l-propranolol (1.2 x 10(-6) to 1.2 x 10(-5) M). Forskolin-induced relaxations of coronary preparations were also antagonized by d,l-propranolol, but those to nitroprusside were not. d-Propranolol also antagonized relaxations to pinacidil but only when used in higher concentrations than the I-isomer. Nadolol and metoprolol, two other beta receptor antagonists with differing profiles of action, also antagonized to some extent the vasodilator action of pinacidil. The known potassium channel antagonist, glibenclamide, shifted the concentration-relaxation curve for pinacidil to the right, but d,l-propranolol produced an additional antagonistic effect in the presence of glibenclamide. Relaxations of contracted tracheal ring preparations of guinea pig by pinacidil, however, were not antagonized by d,l-propranolol, suggesting specificity for vascular tissue. Isoproterenol increased significantly the cyclic AMP levels in coronary tissue, but pinacidil had no such effect, ruling out an adrenergic component to pinacidil action. Pinacidil increased the efflux of 86Rb in isolated coronary preparations, and this effect was blunted by propranolol. It is concluded that beta receptor antagonists inhibit relaxations to a potassium channel opener by a mechanism independent of beta adrenergic receptors and that this effect may have therapeutic implications.
Kalsner
S
S
Department of Physiology, City University of New York Medical School, New York 10031.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology*; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics; D014132:Trachea / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D006146:Guanidines; D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D014665:Vasodilator Agents; D009599:Nitroprusside; D005576:Colforsin; D020110:Pinacidil; D011433:Propranolol; D000242:Cyclic AMP; D005905:Glyburide