Suppression by ethanol of pressor response caused by the inhibition of nitric oxide synthesis.
The effects of ethanol on mean arterial pressure (MAP) and heart rate (HR) responses to the nitric oxide synthase inhibitor, NG-nitro-L-arginine, and to angiotensin II and noradrenaline were studied in rats. I.V. bolus injections of NG-nitro-L-arginine dose dependently increased MAP in vehicle-pretreated rats, with a maximum increase of 56 +/- 7 mm Hg and an ED50 of 3.8 +/- 0.4 mg/kg, respectively. I.v. infusions of ethanol dose dependently reduced maximum MAP response to NG-nitro-L-arginine, with a Ki of 96 +/- 8 mg/kg per min but did not alter the ED50. Ethanol (48 mg/kg per min) did not modify the MAP response to i.v. bolus injections of angiotensin II (0.02-1.28 micrograms/kg) or noradrenaline (0.25-16 micrograms/kg). However, ethanol attenuated the reflex HR responses of NG-nitro-L-arginine and angiotensin II but not that of noradrenaline. The results demonstrate that ethanol selectively but non-competitively inhibits the MAP response to NG-nitro-L-arginine, suggesting an interaction between ethanol and the L-arginine/nitric oxide pathway.
Wang
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Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Pang
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D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000804:Angiotensin II; D019335:Nitroarginine; D009569:Nitric Oxide; D000431:Ethanol; D001120:Arginine; D009638:Norepinephrine