PT  - JOURNAL ARTICLE
AU  - Aman S. Hussain
AU  - Natascha H. Crispino
AU  - Brian E. McLaughlin
AU  - James F. Brien
AU  - Gerald S. Marks
AU  - Kanji Nakatsu
TI  - Glyceryl Trinitrate-Induced Vasodilation Is Inhibited by Ultraviolet Irradiation Despite Enhanced Nitric Oxide Generation: Evidence for Formation of a Nitric Oxide Conjugate
DP  - 1999 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 895--900
VI  - 289
IP  - 2
4099  - http://jpet.aspetjournals.org/content/289/2/895.short
4100  - http://jpet.aspetjournals.org/content/289/2/895.full
SO  - J Pharmacol Exp Ther1999 May 01; 289
AB  - 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 μM 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 μM 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. The American Society for Pharmacology and Experimental Therapeutics