title: Dissimilarity between prostaglandin E1 and nitric oxide donors as potentiators of plasma exudation in the rabbit skin in vivo.
abstract: The ability of prostaglandin E1 (PGE1) and nitric oxide (NO) donor compounds such as sodium nitroprusside (SNP), glyceryl trinitrate (GTN), and 3-morpholino-sydnonimine (SIN-1) to modulate the histamine- and bradykinin-induced increase in microvascular permeability have been investigated in rabbit skin. The effect of the NO synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on the plasma exudation induced by histamine and bradykinin was also studied. Local edema formation was evaluated using [125I]human serum albumin. New Zealand white rabbits received an intravenous injection of [125I]human albumin followed immediately by the intradermal injection of edematogenic agents into the shaved dorsolateral skin. PGE1 (0.1 nmol/site) significantly potentiated both histamine- and bradykinin-induced edema. In contrast, SNP (0.4-400 nmol/site), SIN-1 (0.4-400 nmol/site), and GTN (0.4-40 nmol/site) did not affect the edematogenic response induced by either histamine or bradykinin. GTN (0.4-40 nmol/site) also had no effect on the increase in plasma exudation induced by histamine and bradykinin in the presence of PGE1. L-NAME (50-400 nmol/site, but not its enantiomer D-NAME, dose-dependently reduced the edema formation induced by a combination of either histamine or bradykinin with PGE1. This inhibition was significantly reversed by SNP (4-400 nmol/site) and by high doses (2.5 mumol/site) of L-arginine (but not by D-arginine). Our results thus demonstrate that PGE1, but not nitrovasodilators, can actually potentiate histamine- and bradykinin-induced edema in rabbit skin.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, Campinas (SP), Brazil.
authors.forename: S R
authors.initials: SR
authors.lastname: Mariani-Pedroso
authors.forename: L
authors.initials: L
authors.lastname: Bizeto
authors.forename: E
authors.initials: E
authors.lastname: Antunes
authors.forename: R
authors.initials: R
authors.lastname: Zatz
authors.forename: G
authors.initials: G
authors.lastname: de Nucci
mesh_terms: D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D004487:Edema / Q000139:chemically induced; D005122:Exudates and Transudates / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D012867:Skin / Q000098:blood supply; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D006633:Histamine Antagonists; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; C002385:linsidomine; D006632:Histamine; D001120:Arginine; D008981:Molsidomine; D000527:Alprostadil; D005996:Nitroglycerin; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester