Cyclic GMP regulates cromakalim-induced relaxation in the rat aortic smooth muscle: role of cyclic GMP in K(ATP)-channels.
Recent studies have shown that nitric oxide (NO) modulates K+-channel activity which play an important role in controlling vascular tone. The formation of cyclic guanosine 3',5'-monophosphate (cyclic GMP) has also been recognized to be associated with the vasodilatory effect of NO. Both cyclic GMP and NO increase whole-cell K+-current by activating Ca2+-activated K+-channels (K(Ca)-channels). Here, we show evidence that activators of soluble guanylyl cyclase sodium nitroprusside or 3-morpholino-sydnonimine (SIN-1), and an analogue of cyclic GMP 8-bromo-cyclic GMP enhance the relaxation induced by cromakalim which is blocked by glibenclamide (a specific inhibitor of ATP-sensitive K+-channels [K(ATP)-channels]), and partially attenuated by methylene blue (an inhibitor of cyclic GMP formation). However, this is not due to the increase of cyclic GMP level by cromakalim itself because the relaxation induced by cromakalim is not associated with the changes of cyclic GMP level formed in the aortic smooth muscle. Thus, it is most likely that cyclic GMP also modulates activity of K(ATP)-channels, in addition to K(Ca)-channels, in the rat aorta.
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.
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Wu
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Chen
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Yen
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001013:Aorta, Thoracic; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D018999:Charybdotoxin / Q000494:pharmacology; D019806:Cromakalim / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019806:Cromakalim; D018999:Charybdotoxin; D009599:Nitroprusside; D001030:Apamin; C016276:8-bromocyclic GMP; C002385:linsidomine; D000255:Adenosine Triphosphate; D008981:Molsidomine; D006152:Cyclic GMP; D005905:Glyburide; D002118:Calcium; D008751:Methylene Blue