Effects of isoproterenol on active force and Ca2+ X calmodulin-sensitive phosphodiesterase activity in porcine coronary artery.
Relaxation of vascular smooth muscle following beta-adrenergic stimulation may result from reduction of the cytoplasmic Ca2+ concentration, reduction in the sensitivity of the contractile apparatus to Ca2+, or both. To help resolve these possibilities, we measured the extent of activation of Ca2+ X calmodulin-sensitive phosphodiesterase in intact porcine coronary artery strips as a functional indicator of the cytoplasmic Ca2+ concentration. Both calmodulin-stimulated phosphodiesterase activity and active force increased during K+ stimulation of coronary artery strips. Relaxation of K+-contracted artery strips following stimulus withdrawal was accompanied by rapid inactivation of Ca2+ X calmodulin-sensitive phosphodiesterase. The temporal relationship between isoproterenol-induced relaxation and inactivation of Ca2+ X calmodulin-sensitive phosphodiesterase was studied in both histamine- and K+-contracted tissues. Stimulation of strips with 10 microM histamine or with 44 mM K+ led to comparable increases both in active force and in calmodulin-stimulated phosphodiesterase activity. Thereafter, sustained contraction elicited by histamine was accompanied by a decrease in calmodulin-stimulated phosphodiesterase activity. Isoproterenol rapidly relaxed histamine-contracted strips and accelerated the decrease in phosphodiesterase activity. In contrast, sustained contraction in response to K+ was accompanied by a sustained elevation of calmodulin-stimulated phosphodiesterase activity. Isoproterenol treatment of K+-contracted tissues led to relaxation that was slow and incomplete, and it had very little effect on calmodulin-stimulated phosphodiesterase activity. We conclude that reduction of the cytoplasmic Ca2+ concentration is important for rapid relaxation of the coronary artery following beta-adrenergic stimulation. We cannot disallow the possibility that a decrease in the sensitivity of the contractile apparatus to Ca2+ is involved to some degree.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D013552:Swine
D015105:3',5'-Cyclic-AMP Phosphodiesterases; D007545:Isoproterenol; D011188:Potassium