Vasodilator action of the S-nitrosothiol, SNAP, in rat isolated perfused lung.
The pulmonary vasodilator action of an S-nitrosothiol, S-nitroso acetylpenicillamine (SNAP), was investigated in the rat pulmonary vasculature. The influence of its nitric oxide donator property was studied by comparison with the effect of acetylpenicillamine (AP), SNAP minus the nitroso group, and the blockade of nitric oxide release by the L-arginine analogue, L-NAME. In the isolated rat lung perfused with autologous blood at a constant flow rate (IPL), changes in pulmonary artery pressure (Ppa) reflect changes in pulmonary vascular resistance. Dose-response relationships to both SNAP and AP (0.1, 1, 10 and 100 micrograms) were established both during normoxic ventilation (air + 5% CO2; low Ppa) and when Ppa was raised by alveolar hypoxic vasoconstriction (2% O2 + 5% CO2). SNAP caused small dose-dependent fall in normoxic Ppa (mean +/- S.D. 17.4 +/- 3.0 mm Hg). In 11 rat IPL % fall of Ppa was 1, 3 and 4% for 1, 10 and 100 micrograms, respectively (p < 0.01). This fall was more obvious when Ppa was raised by hypoxia (mean Ppa rise (HPV) 11.5 +/- 3.8 mm Hg); there was a 22, 55 and 79% fall in HPV for 1, 10 and 100 micrograms in 11 rat IPL. The dilatation after 10 micrograms SNAP was not consistently affected by 100 micrograms L-NAME (% fall in HPV pre L-NAME 45 +/- 22% vs 42 +/- 23% post L-NAME). AP had no significant effect on Ppa, causing only small falls in Ppa, equivalent to solvent (saline). There was occasionally a small rise in Ppa with 10 and 100 micrograms AP. Thus, the dilator action of SNAP is most likely due to its NO donator property, and is not consistently affected by blockade of endogenous NO release.
Emery
C J
CJ
Department of Experimental Medicine, University of Sheffield, UK.
D000208:Acute Disease; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D008623:Mercaptoethanol; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine; D026403:S-Nitrosothiols; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D014665:Vasodilator Agents; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine; D019331:NG-Nitroarginine Methyl Ester