Abstract
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 contributed 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 newborn pigs with Nω-monomethyl-L-arginine or specific nNOS inhibitors 7-nitroindazole monosodium, 3-bromo-7-nitroindazole, and 1-(2-trifluoromethylphenyl) imidazole extended the upper limit of CBF autoregulation as seen in saline-treated (control) juvenile (4–6-wk-old) animals. Cerebrovascular production of nitrite (stable NO oxidation product) in vivo was markedly increased during hypertension (mean arterial blood pressure >90 mm Hg) in newborn but not in the juvenile pigs. Inhibition of NOS with Nω-monomethyl-L-arginine, 7-nitroindazole monosodium, 3-bromo-7-nitroindazole, or 1-(2-trifluoromethylphenyl) 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 newborn than in the tissues of juvenile pigs. It is concluded that during acute hypertension, excess production of NO associated with increased activity of NOS curtails the upper limit of CBF autoregulation in the newborn subject; in addition, nNOS seems to serve a significant role in this important physiologic function.
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Abbreviations
- CBF:
-
cerebral blood flow
- NO:
-
nitric oxide
- NOS:
-
nitric oxide synthase
- PG:
-
prostaglandins
- MABP:
-
mean arterial blood pressure
- BP:
-
blood pressure
- L-NMMA:
-
Nω-monomethyl-L-arginine
- 7-NINA:
-
7-nitroindazole monosodium salt
- TRIM:
-
1-(2-trifluoromethylphenyl) imidazole
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Acknowledgements
The authors thank Hensy Fernandez for her technical assistance and F. Ménard Inc. (Ange-Gardien, Quebec) for their generous supply of newborn and juvenile pigs.
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Supported by grants from the Medical Research Council of Canada, the Heart and Stroke Foundation of Quebec, the Hospital for Sick Children's Foundation, and the March of Dimes Birth Defects Foundation. P. Hardy and A-M. Nuyt are recipients of fellowship awards from the Medical Research Council of Canada.
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Hardy, P., Nuyt, AM., Dumont, I. et al. Developmentally Increased Cerebrovascular NO in Newborn Pigs Curtails Cerebral Blood Flow Autoregulation. Pediatr Res 46, 375 (1999). https://doi.org/10.1203/00006450-199910000-00004
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DOI: https://doi.org/10.1203/00006450-199910000-00004
