title: Persistence of effects of nitric oxide synthase inhibitors: comparisons on blood flow and plasma exudation in guinea pig skin.
abstract: Plasma protein extravasation has been measured in guinea pig skin using 125I-albumin and blood flow using 133Xenon (133Xe) clearance. The nitric oxide (NO) synthase inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME), N(G)-monomethyl-L-arginine (l-NMMA) and N(G)-nitro-L-arginine (L-NOArg) and the alpha-adrenoceptor agonist, phenylephrine, inhibited bradykinin induced plasma protein extravasation when co-injected with the peptide. The inhibitory effects of L-NAME and L-NOArg lasted for up to 8 and 4 h, respectively, whereas phenylephrine and L-NMMA had no persistent inhibitory effects. When co-injected with 133Xe, L-NAME, L-NMMA, L-NOArg and phenylephrine, but not D-NAME, produced significant reductions in skin blood flow. When injected prior to 133Xe, L-NAME and L-NOArg, but not phenylephrine or L-NMMA, significantly reduced flow. The effect of L-NAME on flow was not significant at 8 h. Thus, although the inhibitory effects of the NO synthase inhibitors on mediator induced plasma protein extravasation show correlations with their effects on blood flow, the persistent effect of L-NAME on exudation appears to extend beyond its effect on flow.
authors.affiliation: Department of Pharmacology, King's College London, UK.
authors.forename: A C
authors.initials: AC
authors.lastname: Perez
authors.forename: A M
authors.initials: AM
authors.lastname: Khawaja
authors.forename: C P
authors.initials: CP
authors.lastname: Page
authors.forename: W
authors.initials: W
authors.lastname: Paul
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D005122:Exudates and Transudates / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D007457:Iodine Radioisotopes; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012709:Serum Albumin / Q000493:pharmacokinetics; D012867:Skin / Q000098:blood supply* / Q000187:drug effects*; D013237:Stereoisomerism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D012709:Serum Albumin; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester