Glyceryl trinitrate-induced vasodilation is inhibited by ultraviolet irradiation despite enhanced nitric oxide generation: Evidence for formation of a nitric oxide conjugate
As. Hussain et al., Glyceryl trinitrate-induced vasodilation is inhibited by ultraviolet irradiation despite enhanced nitric oxide generation: Evidence for formation of a nitric oxide conjugate, J PHARM EXP, 289(2), 1999, pp. 895-900
Citations number
31
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Our objective was to determine whether a stabilized form of nitric oxide (N
O) such as an S-nitrosothiol, rather than NO itself, is the vasoactive meta
bolite produced when glyceryl trinitrate (GTN) interacts with vascular smoo
th muscle. In a control study, NO formation was measured by a chemiluminesc
ence-headspace gas method during the incubation of a prototype S-nitrosothi
ol, namely, S-nitroso-N-acetylpenicillamine (SNAP), in Krebs' solution. NO
formation from SNAP was increased when the incubation was carried out in th
e presence of UV light, indicating that homolytic photolysis of the S-nitro
sothiol 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 incub
ation. 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 mu M and 10 +/- 6 nM, respectively,
were observed. In the presence of UV light, the vasodilator response of BP
A to SNAP and GTN was attenuated, and EC50 values of 2.7 +/- 3.0 mu M and 4
9 +/- 23 nM, respectively, were observed. Our results are consistent with t
he idea that GTN biotransformation by vascular smooth muscle results in the
production of a stabilized form of NO, possibly an S-nitrosothiol, and tha
t degradation of this metabolite by UV light results in NO formation accomp
anied by decreased vasodilation.