Dissimilarity between prostaglandin E1 and nitric oxide donors as potentiators of plasma exudation in the rabbit skin in vivo.
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)
Mariani-Pedroso
S R
SR
Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, Campinas (SP), Brazil.
Bizeto
L
L
Antunes
E
E
Zatz
R
R
de Nucci
G
G
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*
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