Hypotensive effect of hydroxylamine, an endogenous nitric oxide donor and SSAO inhibitor.
The endogenous compound hydroxylamine relaxes vascular smooth muscle in vitro, apparently through conversion to the vasodilator factor nitric oxide, but its effect on blood pressure has not been characterized. We found that in the anesthetized rat the amine elicits dose-related hypotension when administered by continuous iv infusion. In experiments designed to explore the mechanism of this effect, hydroxylamine was compared with the nitric oxide donor nitroprusside and the direct-acting vasodilator hydralazine, using pretreatments known to modify diverse mechanisms of vasodilation. Hydroxylamine hypotension was enhanced by the SSAO inhibitor isoniazid and the SSAO substrate methylamine, a pattern shared by hydralazine. Responses were blocked by the guanylate cyclase inhibitor methylene blue and were increased by the nitric oxide synthase inhibitor L-NAME, a pattern shared by nitroprusside. It was concluded that hydroxylamine exerts hypotension partly through conversion to nitric oxide and partly by a "hydralazine-like" mechanism involving SSAO inhibition.
Vidrio
H
H
Department of Pharmacology, Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico. vidrio@servidor.unam.mx
Medina
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M
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006830:Hydralazine / Q000494:pharmacology; D019811:Hydroxylamine / Q000378:metabolism / Q000494:pharmacology*; D007022:Hypotension / Q000139:chemically induced* / Q000201:enzymology* / Q000503:physiopathology; D007275:Injections, Intravenous; D007538:Isoniazid / Q000494:pharmacology; D008297:Male; D008744:Methylamines / Q000378:metabolism / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D008744:Methylamines; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009599:Nitroprusside; D006830:Hydralazine; D019811:Hydroxylamine; D009569:Nitric Oxide; C027451:methylamine; D019001:Nitric Oxide Synthase; D006631:Amine Oxidase (Copper-Containing); D006162:Guanylate Cyclase; D007538:Isoniazid