title: Exogenous NO inhibits basal NO release from vascular endothelium in vitro and in vivo.
abstract: This study tested the hypothesis that exogenous nitric oxide (NO) inhibits basal release of NO in isolated rat aortic rings and in vivo. Thoracic aortic rings were suspended in organ chambers with Krebs-Henseleit solution. In untreated rings, the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) markedly increased basal vascular tone by 34.6 +/- 5.2% of maximal force produced by 100 nM thromboxane A2 mimetic U-46619, indicating a basal release of NO. Other rings were pretreated with the exogenous NO donor S-nitroso-N-acetylpenicillamine (SNAP) for 20 min and then washed free of drug. In these rings, L-NAME-induced vasoconstriction was significantly attenuated in a concentration-dependent manner (from 34.6 +/- 5.2 to 25.7 +/- 2.9% at SNAP = 0.5 microM, 15.2 +/- 3.1% at 1 microM, and 11.9 +/- 2.5% at 5 microM), while having no effect on NO-independent phenylephrine-induced vasoconstriction (35.4 +/- 4.7 untreated vs. 41.3 +/- 4.3% SNAP pretreated, not significant). In addition, the nonnitrosylated parent molecule of SNAP, acetylpenicillamine, had no effect on the vasoconstriction induced by L-NAME. In the in vivo studies in anesthetized rats, L-NAME caused significant hypertensive responses (34 +/- 4-mmHg increase in mean arterial blood pressure). Subvasoactive doses of SNAP attenuated these hypertensive responses in a dose-dependent manner (20 +/- 3-mmHg increase with 10 micrograms/kg SNAP pretreatment and 16 +/- 4-mmHg increase with 20 micrograms/kg SNAP pretreatment), but any dose of acetylpenicillamine studied had no effect. Coadministration of superoxide dismutase and SNAP significantly potentiated the inhibitory effect of the NO donor on vasocontraction responses to L-NAME. Furthermore, SNAP did not attenuate the hypertensive responses to phenylephrine. These results indicate that exogenous NO significantly inhibits basal NO release both in vitro and in vivo, suggesting that NO plays an important negative-feedback regulatory role under physiological conditions.
authors.affiliation: Department of Surgery, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5004, USA.
authors.forename: X L
authors.initials: XL
authors.lastname: Ma
authors.forename: B L
authors.initials: BL
authors.lastname: Lopez
authors.forename: T A
authors.initials: TA
authors.lastname: Christopher
authors.forename: D S
authors.initials: DS
authors.lastname: Birenbaum
authors.forename: J
authors.initials: J
authors.lastname: Vinten-Johansen
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D013482:Superoxide Dismutase / Q000494:pharmacology; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D013482:Superoxide Dismutase; D010396:Penicillamine; D019331:NG-Nitroarginine Methyl Ester