Photorelaxation Is Not Attenuated by Inhibition of the Nitric Oxide-cGMP Pathway

Abstract

Photorelaxation of arteries by ultraviolet (UV) light is hypothesized to result from nitric oxide (NO) released from photoactivable stores. Recently, a study reported enhanced photorelaxation of aortic tissue from rats administered the NO synthase (NOS) inhibitor N^ω-nitro-L-arginine (L-NNA). Presumably, the potentiated photorelaxation was due to NO generated from UV-light-induced decomposition of the NO₂ moiety of L-NNA. However, we hypothesized that photorelaxation is: (1) not the result of NO synthesis and subsequent activation of guanylate cyclase and (2) not due to hyperpolarization induced by NO or any other factor. Endothelium-denuded rat aortic rings were suspended in isolated baths for isometric force measurement. Rings were exposed to UV light (366 nm) before addition of phenylephrine or KCI, and then at each agonist concentration during a cumulative concentration response curve. NOS inhibition by L-NNA and L-thiocitrulline, which lacks an NO₂ group, enhanced photorelaxation of basal myogenic tone and contraction to phenylephrine (EC70). Furthermore, relaxation of a maximum phenylephrine-induced contraction to the NO donor S-nitroso-N-acetyl-D L-penicillamine during UV light exposure was not altered by incubation of rings with L-NNA or tissues from animals fed L-NNA. These data demonstrate that NO is not produced endogenously or from the breakdown of L-NNA to result in photorelaxation. Methylene blue (MB) did not alter photorelaxation, suggesting that cGMP is not essential to the response. MB and L-NNA together potentiated photorelaxation of basal myogenic tone and phenylephrine-induced contraction. Photorelaxation of KCl-induced contraction was unaltered, indicating that hyperpolarization does not contribute to the relaxation. Photorelaxation of basal myogenic tone and KCl-induced contraction excludes the possibility that UV light is interfering with agonist-receptor binding. Collectively, these results refute the hypotheses that photorelaxation results from activation of the NO-cGMP pathway, release of a hyperpolarization factor, or inhibition of drug-receptor interaction. Interestingly, photorelaxation may be inhibited by NO-cGMP pathway activation, uncovering a novel effect of this messenger system on vascular reactivity.

A photosensitive vascular smooth muscle store of nitric oxide in mouse aorta: no dependence on expression of endothelial nitric oxide synthase

“…Once released, NO targets the haem moiety of soluble guanylate cyclase (sGC) in vascular smooth muscle cells, and thus, activates sGC, leading to an increase in cGMP which acts as a second messenger in a cascade of phosphorylation events resulting in vasodilation. It has been reported that ODQ and methylene blue, inhibitors of sGC, reduce photorelaxation (Charpie et al ., 1994; Furchgott et al ., 1985; Lovren & Triggle, 1998), have no effect (Goud et al ., 1996) or even potentiate photorelaxation (Chen & Gillis, 1993). Furthermore, it has been shown that photorelaxation increases cGMP levels in rabbit and rat aortae through the activation of sGC (Karlsson et al ., 1984; Furchgott et al ., 1985; Chen & Gillis, 1992).…”

Heat and Photolytic Nitric Oxide are Essential Factors for Light-induced Vascular Tension Changes

“…chemical structure of these NOS inhibitors, resulting in NO release. Goud et al [13] refute the NO 2 group hypothesis by observing an enhancement of photorelaxation in the presence of NOS inhibitors which have no NO 2 group. However, our results support the NO 2 group hypothesis.…”

“…Therefore, the NO may be exogenously generated by a photochemical reaction rather than by endogenous NOS in the endothelium. Goud et al [13] suggested that photorelaxation is not attenuated by inhibition of the NO-cGMP pathway, and refuted the NO hypothesis. However, it is possible that their dose of MB (10 6 mol/l) was insu$cient.…”

“…Kubaszewski et al [12] found that UV light causes NO to be released from the vascular ring during photorelaxation. Recently, some evidence to refute this NO hypothesis has been demonstrated in a study [13] showing that GC inhibition by methylene blue (MB) does not alter photorelaxation.…”

Transepidermal Water Loss During Halogen Spotlight Phototherapy in Preterm Infants

“…The pathway of this mechanism is still not completely solved, but there is evidence of involvement of so-called nitrosothiols. Whereas for a long time nitric oxide was thought to be the active compound in photorelaxation (31), various recent studies have pointed out that S-nitrosothiols account for the relaxation in vascular smooth muscle cells (32)(33)(34)(35), both by nitric oxide release and by direct binding to nitrosothiol recognition sites (33). This is an attractive hypothesis for the increase of skin blood flow in infants receiving phototherapy, as nitrosothiol isomers can suppress baroreceptor reflexes in the aortic arch (33).…”