Vasodilator responses to acetylcholine, bradykinin, and substance P are mediated by a TEA-sensitive mechanism.
The effects of tetraethylammonium (TEA), a K+ channel antagonist, on vasodilator responses were investigated in the hindquarters vascular bed of the cat under constant-flow conditions. After administration of TEA in a total dose of 60 mg/kg into the hindquarters perfusion circuit, vasodilator responses to acetylcholine, bradykinin, and substance P were reduced, whereas vasodilator responses to the NO donors, diethylamine-NO complex, S-nitroso-N-acetylpenicillamine, and sodium nitroprusside, and to prostaglandin E1, albuterol, vasoactive intestinal polypeptide, isradipine, and levcromakalim were not altered. The inhibitory effect of TEA on responses to the endothelium-dependent vasodilators was reversible with time, and vasoconstrictor responses to norepinephrine, U-46619, angiotensin II, and BAY K 8644 were enhanced by the K+ channel antagonist. Although TEA had no sustained effect on baseline systemic arterial and hindquarters perfusion pressures, the NO synthase inhibitor, N omega-nitro-L-arginine methyl ester, increased these pressures in the presence of TEA. The results of the present investigation suggest that TEA attenuates vasodilator responses to acetylcholine, bradykinin, and substance P by inhibiting the release of endothelium-derived relaxing factor. These data suggest that the acetylcholine-, bradykinin-, and substance P-stimulated release of endothelium-derived relaxing factor may involve the opening of a TEA-sensitive K+ channel in the endothelium in the hindlimb vascular bed of the cat, but that a TEA-sensitive mechanism is not involved in the maintenance of baseline tone in this vascular bed.
Champion
H C
HC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Kadowitz
P J
PJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology*; D002415:Cats; D019806:Cromakalim; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006614:Hindlimb / Q000098:blood supply; D006834:Hydrazines / Q000494:pharmacology; D017275:Isradipine / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009589:Nitrogen Oxides; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D013373:Substance P / Q000494:pharmacology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D006834:Hydrazines; D009589:Nitrogen Oxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011758:Pyrroles; D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D019806:Cromakalim; D000804:Angiotensin II; D009599:Nitroprusside; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013928:Thromboxane A2; D019789:Tetraethylammonium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D026423:S-Nitroso-N-Acetylpenicillamine; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D000527:Alprostadil; D010396:Penicillamine; D000109:Acetylcholine; D000420:Albuterol; D001920:Bradykinin; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D017275:Isradipine