Inhibitory mechanism of N(G)-nitro-L-arginine on acetylcholine-induced depressor responses in dogs.
The significance of the blood pressure elevation caused by N(G)-nitro-L-arginine (L-NNA) to inhibitory mechanism of the drug on depressor responses to acetylcholine in anesthetized dogs was investigated. L-NNA (50 mg kg(-1), i.v.) elevated blood pressure to a plateau of 30-50 mm Hg above baseline level and shifted the dose-response curve for acetylcholine-induced responses to the right by about 70-fold. Prevention by hydralazine (1 mg kg(-1), i.v.) of the blood pressure elevation over baseline level caused by L-NNA attenuated the inhibitory effect of L-NNA on the responses to acetylcholine. Intravenous neostigmine (30 microg kg(-1) bolus followed by 15 microg kg(-1) min(-1)) attenuated the inhibitory effect of L-NNA. The magnitude of the rightward shift in the dose-response curve for carbachol-induced depressor responses was only 3-fold. These results suggest that the accelerated acetylcholine metabolism by blood pressure elevation contributes to a considerable degree to the inhibitory mechanism of L-NNA.
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Tokyo, Japan.
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T
Nakahara
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Nejishima
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Nakayama
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K
Ishii
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D002802:Cholinesterases / Q000097:blood / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D009388:Neostigmine / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D002273:Carcinogens; D018678:Cholinergic Agents; D004791:Enzyme Inhibitors; D006834:Hydrazines; D014665:Vasodilator Agents; D019335:Nitroarginine; C029424:hydrazine; D009388:Neostigmine; D001285:Atropine; D002217:Carbachol; D002802:Cholinesterases; D000109:Acetylcholine