Role of Na(+)-Ca2+ exchange in the regulation of vascular smooth muscle tension.
To determine the role of the Na(+)-Ca2+ exchange systems of nerve terminal and sarcolemmal membrane on development of tension in rabbit aortic rings, internal or external Na+ concentration was changed with either ouabain or Na(+)-free solution, respectively. Ouabain produced a verapamil-insensitive but external Na(+)- and Ca(2+)-dependent biphasic tension with distinct lag periods both of which were shortened by depolarization with KCl. The first phase of tension was inhibited by prazosin, phentolamine, in vitro neurolysis with 6-hydroxydopamine and in vivo treatment with reserpine to deplete catecholamines in nerve terminals. Therefore, first phase of tension was attributed to catecholamines released from nerve terminals induced by increased axoplasmic Ca2+ concentration mediated by the neural Na(+)-Ca2+ exchanger due to the increased axoplasmic Na+ concentration resulting from inhibition of the Na(+)-Ka+ pump with ouabain. In the absence of the first phase of tension, the second phase of tension was enhanced by caffeine, presumably by preventing sequestration of the sarcolemmal Na(+)-Ca2+ exchanger-mediated increase in cytosolic Ca2+ concentration in vascular smooth muscle cells. The prazosin-insensitive tension was dependent on the external Na+ concentration and was also attributed to the sarcolemmal Na(+)-Ca2+ exchanger of vascular smooth muscle. The magnitude of the increase in tension with ouabain or Na(+)-free solution attributed to the sarcolemmal Na(+)-Ca2+ exchanger of vascular smooth muscle was larger than that mediated by the exchanger of the nerve terminal. It was concluded that the Na(+)-Ca2+ exchange systems of both the nerve terminal and the vascular smooth muscle sarcolemma contribute to the development of tension by different mechanisms and to different extents when internal or external Na+ concentration was changed.
Motley
E D
ED
Department of Pharmacology, University of Cincinnati College of Medicine, Ohio 45267.
Paul
R J
RJ
Matlib
M A
MA
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002352:Carrier Proteins / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000201:enzymology / Q000502:physiology / Q000648:ultrastructure; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009411:Nerve Endings / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D012508:Sarcolemma / Q000201:enzymology / Q000502:physiology / Q000648:ultrastructure; D012964:Sodium / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology
D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D002110:Caffeine; D010042:Ouabain; D012964:Sodium; D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D011224:Prazosin; D010646:Phentolamine