Developmentally increased cerebrovascular NO in newborn pigs curtails cerebral blood flow autoregulation

We tested the hypothesis that a reduced ability of the newborn (1-2 d old) to autoregulate cerebral blood flow (CBF) during acute hypertension is cont ributed by an increased synthesis of nitric oxide (NO) from endothelial (e) and neuronal NO synthase (nNOS). As previously reported, CBF (measured by radiolabeled microsphere technique) in newborn pigs remained constant only between 50 and 90 mm Hg of mean arterial blood pressure. Treatment of newbo rn pigs with N-omega-monomethyl-L-arginine or specific nNOS inhibitors 7-ni troindazole monosodium, 3-bromo-7-nitroindazole, and 1-(2-trifluoromethylph enyl) imidazole extended the upper limit of CBF autoregulation as seen in s aline-treated (control) juvenile (4-6-wk-old) animals. Cerebrovascular prod uction of nitrite (stable NO oxidation product) in vivo was markedly increa sed during hypertension (mean arterial blood pressure >90 mm Hg) in newborn but not in the juvenile pigs. Inhibition of NOS with N-omega-monomethyl-L- arginine, 7-nitroindazole monosodium, 3-bromo-7-nitroindazole, or 1-(2-trif luoromethylphenyl) imidazole prevented the hypertension-induced increase in nitrite levels. In addition, eNOS and nNOS protein expression and activity were 2- to 3-fold higher (p < 0.05) in the cerebral microvasculature of ne wborn than in the tissues of juvenile pigs. It is concluded that during acu te hypertension, excess production of NO associated with increased activity of NOS curtails the upper limit of CBF autoregulation in the newborn subje ct; in addition, nNOS seems to serve a significant role in this important p hysiologic function.