Early and late contraction induced by ouabain in human umbilical arteries.
1. Ouabain (3 x 10(-7)-10(-4) M) evoked a biphasic contraction in human umbilical artery that consisted of an early and a late contraction. The Ca(2+)-antagonists, verapamil (10(-7)-10(-5)) M), diltiazem (10(-7)-(10(-5)) M) and nifedipine (10(-9)-10(-7)) M) inhibited the early but not the late contraction. Caffeine (5 mM) changed neither the magnitude of the peak of the biphasic contraction nor the time needed to reach it. 2. Sodium concentration reduction (140 to 0 mM, replaced by N-methyl-D-glucamine, NMG) produced dose-dependent contraction of the arterial strip in 2.5 mM Ca2+ solution after the first treatment with verapamil (10(-5) M) and caffeine (5 mM), but not in Ca(2+)-free solution. 3. After prior treatment with verapamil and caffeine, the amplitude of the ouabain (10(-4) M)-induced late contraction varied, depending on the concentration of Ca2+ (0-2.5 mM) in the medium. 4. Amiloride (5 x 10(-5) M-5 x 10(-4) M), an inhibitor of the Na(+)-Ca2+ exchange system, produced dose-dependent inhibition of the late contraction induced by ouabain (10(-5) M) after prior treatment with verapamil and caffeine. 5. The time needed to reach the peak tension induced by monensin (5 x 10(-7) M) together with ouabain (10(-6) M) was less than that with ouabain alone, but the magnitude of the peak tension was not changed. 6. These results suggest that the early and late contractions caused by ouabain respectively produce a Ca2+ influx through voltage-sensitive Ca2+ channels and Ca2+ entry through sodium-calcium (Na(+)-Ca2+) exchange.
Sato
K
K
Second Department of Internal Medicine, Nagoya City University Medical School, Japan.
Aoki
K
K
D000328:Adult; D000584:Amiloride / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008985:Monensin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology*; D011247:Pregnancy; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004533:Egtazic Acid; D010042:Ouabain; D000584:Amiloride; D008985:Monensin; D012964:Sodium; D014700:Verapamil; D002118:Calcium