Effects of insulin on vasoconstriction induced by thromboxane A2 in porcine coronary artery.
To elucidate the role of insulin in the control of coronary artery tone, its effects on porcine coronary artery contraction evoked by thromboxane A2 (TXA2) were studied in vitro. Ring preparations of porcine proximal coronary artery were suspended in a Magnus apparatus filled with Tyrode's solution at 37 degrees C and aerated with 100% O2, and the isometric tension of the contractions was measured. Insulin itself caused neither contraction nor relaxation. Insulin had no significant effect on the coronary artery contractions evoked by 20 mM K+, norepinephrine, histamine, and serotonin; however, 120 minutes of preincubation with a physiological concentration of insulin (30-300 muunits/ml) significantly accentuated coronary artery contractions evoked by STA2 (10(-11) to 10(-7) M), a stable analogue of TXA2 that is known to act on TXA2/prostaglandin H2 receptors (141.4 +/- 10.9% of the control at 10(-7) M STA2 in the presence of 300 muunits/ml insulin; p less than 0.01). The enhancing effects of insulin on the STA2-induced contractions were affected by extracellular glucose or magnesium ion concentrations. The enhancing effects of insulin were observed only at the glucose concentrations of 100-300 mg/dl and magnesium concentrations of 0.5-1.5 mM. Therefore, insulin was suspected of enhancing TXA2-induced contraction through a process that depends on extracellular glucose and Mg2+.
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
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Yanagisawa-Miwa
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Ito
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Sugimoto
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004347:Drug Interactions; D005947:Glucose / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D007328:Insulin; D012701:Serotonin; D013928:Thromboxane A2; C037866:STA 2; D006632:Histamine; D008274:Magnesium; D005947:Glucose; D011188:Potassium; D009638:Norepinephrine