Hypocapnic constriction in rabbit basilar artery in vitro: triggering by N(G)-monomethyl-L-arginine monoacetate and dependence on endothelin-1 and alkalosis.
This study tested whether hypocapnic constriction of the rabbit basilar artery in vitro can be triggered by a nitric oxide (NO) synthase inhibitor, and whether the resulting constriction is (1) due to the alkaline pH associated with hypocapnia, and (2) endothelin-1 mediated. Hypocapnic (25 mM NaHCO(3); pH 7.76; pCO(2) 14.2) or isocapnic alkaline solution (50 mM NaHCO(3); pH 7.73; pCO(2) 35.0) rarely altered basal tension. N(G)-monomethyl-L-arginine monoacetate (L-NMMA; 0.1 mM) challenge in hypocapnic or isocapnic alkaline solution resulted in near maximal tension that was maintained for 2-2.5 h even following L-NMMA washout. L-NMMA challenge in normal solution (25 mM NaHCO(3); pH 7. 42; pCO(2) 36.9) also induced near maximal tension, although the tension was maintained for only 25 min (mean). Ac-D-Bhg-L-Leu-Asp-L-Ile-L-Ile-L-Trp (PD145065), homopiperidinyl-CO-Leu-D-Trp(CHO)-D-Trp (BQ610), and N-cis-2, 6-dimethyl-piperidinocarbonyl L-gamma-MeLeu-D-Trp (COOCH(3))-Nle (BQ788; 1-3 microM), endothelin ET(A)/ET(B), endothelin ET(A), and endothelin ET(B) receptor antagonists, respectively, completely relaxed the tension that resulted from L-NMMA challenge in hypocapnic or isocapnic alkaline solution. These results demonstrate that constriction due to hypocapnia in vitro can be triggered by an NO synthase inhibitor and is endothelin-1 mediated. Additionally, alkaline pH in the absence of decreased pCO(2) is sufficient to elicit the constriction.
Department of Neurosurgery, University of Cincinnati College of Medicine, and Veterans Affairs Medical Center, 231 Bethesda Avenue, Cincinnati, OH 45267-0515, USA.
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Lee
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Rapoport
D000109:Acetylcholine / Q000494:pharmacology; D000468:Alkalies / Q000494:pharmacology; D000471:Alkalosis / Q000503:physiopathology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000503:physiopathology*; D002245:Carbon Dioxide / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016857:Hypocapnia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D012996:Solutions / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000468:Alkalies; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D012996:Solutions; D014665:Vasodilator Agents; C087220:BQ 610; D002245:Carbon Dioxide; C082887:PD 145065; D019323:omega-N-Methylarginine; C086539:BQ 788; D010208:Papaverine; D000109:Acetylcholine