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Glyceryl Trinitrate-Induced Vasodilation Is Inhibited by Ultraviolet Irradiation Despite Enhanced Nitric Oxide Generation: Evidence for Formation of a Nitric Oxide Conjugate

1999; American Society for Pharmacology and Experimental Therapeutics; Volume: 289; Issue: 2 Linguagem: Inglês

10.1016/s0022-3565(24)38216-3

1521-0103

A S Hussain, N H Crispino, Brian E. McLaughlin, James F. Brien, Gerald S. Marks, Kanji Nakatsu,

Pulmonary Hypertension Research and Treatments

Our objective was to determine whether a stabilized form of nitric oxide (NO) such as an S-nitrosothiol, rather than NO itself, is the vasoactive metabolite produced when glyceryl trinitrate (GTN) interacts with vascular smooth muscle. In a control study, NO formation was measured by a chemiluminescence-headspace gas method during the incubation of a prototype S-nitrosothiol, namely, S-nitroso-N-acetylpenicillamine (SNAP), in Krebs' solution. NO formation from SNAP was increased when the incubation was carried out in the presence of UV light, indicating that homolytic photolysis of the S-nitrosothiol had occurred. When GTN was incubated with bovine pulmonary artery (BPA) in the absence of UV light, NO was not measurable until 5 min of incubation. By contrast, in the presence of UV light, NO was measurable as early as 0.5 min, and by 5 min, it was higher than that observed in the absence of UV light. BPA rings were relaxed with SNAP and GTN in the absence of UV light, and EC50 values of 0.24 +/- 0.28 microM and 10 +/- 6 nM, respectively, were observed. In the presence of UV light, the vasodilator response of BPA to SNAP and GTN was attenuated, and EC50 values of 2.7 +/- 3.0 microM and 49 +/- 23 nM, respectively, were observed. Our results are consistent with the idea that GTN biotransformation by vascular smooth muscle results in the production of a stabilized form of NO, possibly an S-nitrosothiol, and that degradation of this metabolite by UV light results in NO formation accompanied by decreased vasodilation.