title: The endothelium-dependent, substance P relaxation of porcine coronary arteries resistant to nitric oxide synthesis inhibition is partially mediated by 4-aminopyridine-sensitive voltage-dependent K+ channels.
abstract: We examined the role of K+ channels in the endothelium-dependent relaxation which is resistant to nitric oxide (NO) synthase inhibition in porcine coronary artery. In the presence of 0.2 mM NG-nitro-L-arginine (L-NNA), a potent inhibitor of NO synthase, 10 nM substance P (SP) added to 9,11-dideoxy-11alpha,9alpha-epoxymethano-prostaglandin F2alpha (U46619) contractures elicited a relaxation. The L-NNA-resistant relaxation induced by SP was strongly inhibited by 5 mM tetrabutylammonium chloride (TBA), a non-specific inhibitor of K+ channels. Interestingly, 4-aminopyridine (4-AP, 1 mM), a relatively specific inhibitor of voltage-sensitive K+ channels, shortened the duration of SP response, but it had no effect on the peak of SP response. Although 4-AP has also been shown to inhibit Ca2+-activated K+ channels, the shortening effect of 4-AP in SP response was observed in the presence of 1 microM apamin, an inhibitor of small conductance Ca2+-activated K+ channels, or 100 nM charybdotoxin, and inhibitor of large conductance Ca2+-activated K+ channels. Moreover, although SP stimulates both L-NNA-resistant relaxation and endothelium-derived NO-dependent relaxation (EDNO) in porcine coronary arteries, a low concentration of 4-AP (1 mM) affected only the L-NNA-resistant response, but not the EDNO response. These are the first results to show that the L-NNA-resistant relaxation induced by SP, probably, endothelium-derived hyperpolarizing factor(s) (EDHF) response, is dependent on voltage-dependent K+ channels in porcine coronary artery.
authors.affiliation: Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, OH 45267-0576, USA.
authors.forename: S
authors.initials: S
authors.lastname: Shimizu
authors.forename: R J
authors.initials: RJ
authors.lastname: Paul
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D018999:Charybdotoxin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D007537:Isometric Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D015221:Potassium Channels / Q000145:classification / Q000187:drug effects*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D013552:Swine
chemical_list: D004791:Enzyme Inhibitors; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; D018999:Charybdotoxin; D019335:Nitroarginine; D001030:Apamin; D009569:Nitric Oxide; D013373:Substance P; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015761:4-Aminopyridine; C009405:tetrabutylammonium; D019001:Nitric Oxide Synthase; D005905:Glyburide; D002118:Calcium