Nitroglycerin relaxes canine coronary arterial smooth muscle without reducing intracellular Ca2+ concentrations measured with fura-2.
1. Changes in cytoplasmic Ca2+ concentration ([Ca2+]1) were measured simultaneously with force by a microfluorometric method using a calcium indicator, fura-2, in canine coronary arterial smooth muscle cells. 2. Depolarization by high (30-90 mM) KCl-physiological salt solution (PSS) produced concentration-dependent increases in force and [Ca2+]i. 3. The KCl-induced increase in [Ca2+]i abolished by Ca2+-free conditions and almost abolished by verapamil 10-5 M, suggesting that it was entirely due to the increased Ca2+ influx through voltage-dependent Ca2+ channels. 4. The [Ca2+]i force relationship in the presence of verapamil was not distinguishable from that of control. 5. Nitroglycerin produced a concentration-dependent, reversible contraction of the coronary artery that had been contracted by high KCl-PSS, without reduction of the increased [Ca2+]i. 6. The KCl-induced increase in [Ca2+]i was not affected by nitroglycerin and in a presence of nitroglycerin it was abolished by 10-5 M verapamil suggesting that it was caused by the influx of extracellular Ca2+. 7. The [Ca2+]-force curve was shifted to the right by nitroglycerin. 8. It is likely that nitroglycerin relaxes the coronary arterial smooth muscle b reducing the amount of myosin light chain phosphorylation even in the presence of raised [Ca2+]i produced by increased Ca2+ influx following depolarization.
Yanagisawa
T
T
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Kawada
M
M
Taira
N
N
D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D005260:Female; D016257:Fura-2 / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D014700:Verapamil / Q000494:pharmacology
D001572:Benzofurans; C049925:fura-2-am; D011189:Potassium Chloride; D014700:Verapamil; D005996:Nitroglycerin; D002118:Calcium; D016257:Fura-2