A photosensitive vascular smooth muscle store of nitric oxide in mouse aorta: no dependence on expression of endothelial nitric oxide synthase.
(1) Photorelaxation is the reversible relaxation of vascular smooth muscle (VSM) when irradiated with ultraviolet (UV) light resulting from the release of nitric oxide (NO). In this study we characterize the involvement of endothelial nitric oxide synthase (eNOS) in the photorelaxation response of thoracic aorta from endothelial NOS deficient (-/-) and control (C57BL/6j) mice. (2) Cirazoline contracted aortae were repeatedly exposed to 30 s of UV light every 3-4 min. Equal levels of photorelaxation (45+/-2%; n=34) was observed in both strains. (3) 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), K(+), 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), 4-aminopyridine (4-AP) and ethacrynic acid significantly reduced the photorelaxation response. In C57BL/6j mice diethyldithiocarbamate (DETCA) also reduced photorelaxation. (4) Control endothelium-intact and -denuded aorta and L-NAME (100 micro M) treated and untreated eNOS (-/-) aortae were repeatedly exposed to UV light for 5 min every 10 min until no photorelaxation response was observed. After 1 h of rest in the dark the vessels showed between 30-70% recovery of the photorelaxation response indicating regeneration of the store in the absence of the endothelium and eNOS. (5) The results of this study suggest that photorelaxation in mouse aorta VSM results from the release of NO from a stable store of RSNOs, which activates soluble guanylate cyclase (sGC), leading to cGMP-dependent relaxation that is partially mediated by an increase in K(V) channel activation and hyperpolarization. In addition, the eNOS isoform is not essential for the formation of the photorelaxation store and a non-NOS source of NO may be involved in the maintenance of this store.
Andrews
Karen L
KL
Smooth Muscle Research Group, 3330 Hospital Dve, NW, University of Calgary, Calgary, Alberta, Canada, T2N 4N1.
McGuire
John J
JJ
Triggle
Chris R
CR
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology* / Q000528:radiation effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000528:radiation effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics / Q000528:radiation effects; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D014466:Ultraviolet Rays; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse