Guanylate cyclase and not ATP-dependent K(+) channels seems temperature-dependent in smooth muscle relaxation of human umbilical arteries.
The effects of K(+) channel opener, nicorandil [N-(2-hydroxyethyl)-nicotinamide nitrate], on isolated human umbilical arteries were investigated at two temperatures: 37 degrees C and 25 degrees C. The purpose of this investigation was: (1) to confirm the relaxant effect of nicorandil, (2) to elucidate the influence of endothelium and temperature on nicorandil-induced relaxation, (3) to determine which of guanylate cyclase or ATP-sensitive K(+) channels was implicated in temperature-induced relaxation of smooth muscles. Rings, 3-mm-wide, were suspended in organ chambers for isometric force measurement. All solutions were aerated with 95% O(2)-5% CO(2) and maintained at 37 degrees C or 25 degrees C (cooling), pH 7.4. The presence of an intact endothelium was confirmed by immunohistochemistry. During the first set of experiments after contraction with 5-hydroxytryptamine (5-HT 10(-5) M), nicorandil (10(-9)-10(-4) M) was added to the organ chambers with controls and in with rings incubated with L-arginine, N-nitro-L-arginine (L-NNA) an inhibitor of nitric oxide (NO) synthase, [1-H-(1,2,4) oxadiazole (4,3-a) quinoxalin-1-one] (ODQ), a specific inhibitor of guanylate cyclase, or glibenclamide, an antagonist of nicorandil, all at 10(-5) M. In another set of experiments, rings were contracted with 5-HT (10(-5) M) and relaxed with 3-morpholinosydnonimine [SIN-1 (10(-9)-3x10(-5) M) or cromakalim (10(-9)-3x10(-5) M)]. Our results showed that nicorandil induced concentration-dependent relaxation. At 37 degrees C, in the control, the maximum relaxation was 90+/-5%, and 60+/-8% at 25 degrees C (P<0.01). However, the relaxation at 37 degrees C or 25 degrees C remained unchanged after pretreatment with L-arginine, L-NNA, this suggests that the same concentration of drugs used in this type of vessel does not appear to modulate the relaxant effect of nicorandil. On the other hand, we observed that the relaxant effect of SIN-1 was 72+/-5% at 37 degrees C and only 28+/-7% at 25 degrees C (P<0.01). However, relaxations with cromakalim were partly influenced by cooling. In the presence of ODQ, the nicorandil-induced relaxation observed at 37 degrees C or 25 degrees C was less than that in the control and in the rings incubated with glibenclamide. These results for human umbilical arteries indicate that cooling decreases the relaxation response of smooth muscles and that this is partly due to a decreased response to guanylate cyclase.
Tiritilli
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Laboratoire de Physiologie et Pharmacologie Cardiovasculaire, Centre Hospitalier, 20, Rue Armagis 78104 Saint-Germain-en-Laye, France. tiritillialb@aol.com
D000255:Adenosine Triphosphate / Q000502:physiology; D001120:Arginine / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D020108:Nicorandil / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D011247:Pregnancy; D011810:Quinoxalines / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013696:Temperature; D014469:Umbilical Arteries / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D010069:Oxadiazoles; D015221:Potassium Channels; D011810:Quinoxalines; D014665:Vasodilator Agents; D019806:Cromakalim; D019335:Nitroarginine; D020108:Nicorandil; D012701:Serotonin; C002385:linsidomine; D000255:Adenosine Triphosphate; D001120:Arginine; D008981:Molsidomine; D006162:Guanylate Cyclase; D005905:Glyburide