Major role for neuronal NO synthase in curtailing choroidal blood flow autoregulation in newborn pig.
We examined whether nitric oxide (NO) generated from neuronal NO synthase (nNOS) contributes to the reduced ability of the newborn to autoregulate retinal blood flow (RBF) and choroidal blood flow (ChBF) during acute rises in perfusion pressure. In newborn pigs (1-2 days old), RBF (measured by microsphere) is autoregulated over a narrow range of perfusion pressure, whereas ChBF is not autoregulated. N(G)-nitro-L-arginine methyl ester (L-NAME) or specific nNOS inhibitors 7-nitroindazole, 3-bromo-7-nitroindazole, and 1-(2-trifluoromethyl-phenyl)imidazole as well as ganglionic blocker hexamethonium, unveiled a ChBF autoregulation as observed in juvenile (4- to 6-wk old) animals, whereas autoregulation of RBF in the newborn was only enhanced by L-NAME. All NOS inhibitors and hexamethonium prevented the hypertension-induced increase in NO mediator cGMP in the choroid. nNOS mRNA expression and activity were three- to fourfold higher in the choroid of newborn pigs than in tissues of juvenile pigs. It is concluded that increased production of NO from nNOS curtails ChBF autoregulation in the newborn and suggests a role for the autonomic nervous system in this important hemodynamic function, whereas, for RBF autoregulation, endothelial NOS seems to exert a more important contribution in limiting autoregulation.
Hardy
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Department of Pediatrics, Research Center of Hôpital Sainte-Justine, 3175 Côte Sainte-Catherine, Montréal H3T 1C5, Québec, Canada.
Lamireau
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Hou
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Dumont
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Abran
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Nuyt
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Varma
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Chemtob
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D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001784:Blood Gas Analysis; D002831:Choroid Plexus / Q000098:blood supply*; D006152:Cyclic GMP / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D023282:Nuclease Protection Assays; D012333:RNA, Messenger / Q000096:biosynthesis; D012039:Regional Blood Flow / Q000502:physiology; D012171:Retinal Vessels / Q000187:drug effects; D013552:Swine
D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP