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 ret inal blood flow (RBF) and choroidal blood flow (ChBF) during acute rises in perfusion pressure. In newborn pigs (1-2 days old), RBF (measured by micro sphere) is autoregulated over a narrow range of perfusion pressure, whereas ChBF is not autoregulated. N-G-nitro-L-arginine methyl ester (L-NAME) or s pecific nNOS inhibitors 7-nitroindazole, 3-bromo-7-nitroindazole, and 1-(2- trifluoromethyl-phenyl)imidazole as well as ganglionic blocker hexamethoniu m, 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-ind uced increase, in NO mediator cGMP in the choroid. nNOS mRNA expression and activity were three- to fourfold higher in the choroid of newborn pigs tha n in tissues of juvenile pigs. It is concluded that increased production of NO from nNOS curtails ChBF autoregulation in the newborn and suggests a ro le for the autonomic nervous system in this important hemodynamic function, whereas, for RBF autoregulation, endothelial NOS seems to exert a more imp ortant contribution in limiting autoregulation.