Neuronal NOS-dependent dilation to flow in coronary arteries of male eNOS-KO mice.
Flow-induced dilation was examined in isolated coronary arteries of endothelial nitric oxide (NO) synthase knockout mice (eNOS-KO) and wild-type (WT) mice. The basal tone of arteries (percentage of passive diameter) was significantly greater in eNOS-KO than in WT mice; their flow-induced dilations, however, were similar. Endothelial removal eliminated the dilations in vessels of both strains of mice. In arteries of WT mice, N(omega)-nitro-L-arginine methyl ester (L-NAME) (10(-4) M) or indomethacin (10(-5) M) alone, inhibited flow-induced dilation by approximately 50%, whereas their simultaneous administration abolished the responses. In arteries of eNOS-KO mice, flow-induced dilation was inhibited by approximately 40% with L-NAME. The residual portion (60%) of the response was eliminated by the additional administration of indomethacin. 7-Nitroindazole (10(-4) M) attenuated flow-induced dilation by approximately 40% in arteries of eNOS-KO mice, but did not affect responses in those of WT mice. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (3 x 10(-5) M) inhibited the L-NAME/7-nitroindazole-sensitive portion of the responses in arteries of eNOS-KO mice. Immunohistochemical evidence confirms the presence of neuronal NOS (nNOS) in the arterial endothelium of eNOS-KO mice. In conclusion, nNOS-derived NO, via activation of cGMP, together with prostaglandins, maintains flow-induced dilation in coronary arteries of male eNOS-KO mice.
Huang
An
A
Department of Physiology, New York Medical College, Valhalla, New York 10595, USA. An_Huang@nymc.edu
Sun
Dong
D
Shesely
Edward G
EG
Levee
Ellen M
EM
Koller
Akos
A
Kaley
Gabor
G
D000818:Animals; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000201:enzymology; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011453:Prostaglandins / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology*
D011453:Prostaglandins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse; D006152:Cyclic GMP