Substance P induces biphasic endothelium-dependent relaxations in pig and rabbit carotid arteries.
Careful handling and preparation of freshly harvested vessels from 22 pigs and 12 rabbits revealed a two-phase vasorelaxation response to cumulative doses of substance P (SP). A rapid, transient relaxation was observed during the cumulative dose-response and a new plateau of equilibrium was seen following an increase in developed force after the last dose of SP. The phase 2 response is also produced by submaximal doses of SP and is not altered by pretreatment of the rings with Indomethacin. Acetylcholine (ACh) caused an endothelium-dependent relaxation but without evidence of a phase 2 plateau. N omega-Nitro-L-Arginine (L-NNA) and N omega-Nitro-L-Arginine Methylester (L-NAME) pretreatment resulted in a shift to the right in the phase 1 response to SP and a complete blockade of phase 2. Methylene blue caused nearly complete block of both phases. Nitroglycerin caused a dose-dependent and prolonged vasorelaxation with no phase 2.
Gross
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DR
Department of Surgery, University of Kentucky College of Medicine, Lexington 40536-0084.
Fiscus
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Arden
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Maley
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Lanzo
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Salley
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D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002339:Carotid Arteries / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D005996:Nitroglycerin / Q000494:pharmacology; D011817:Rabbits; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D013373:Substance P; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D005996:Nitroglycerin; D000109:Acetylcholine; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin