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Am J Physiol Regul Integr Comp Physiol 284: R734-R741, 2003. First published December 5, 2002; doi:10.1152/ajpregu.00510.2002
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Vol. 284, Issue 3, R734-R741, March 2003

Maturation depresses mouse cerebrovascular tone through endothelium-dependent mechanisms

Greg G. Geary, John N. Buchholz, and William J. Pearce

Departments of Physiology and Pharmacology, Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, California 92354

In light of previous observations that the range of arterial pressures over which cerebral blood flow is autoregulated differs dramatically in neonates and adults, the present experiments explored the hypothesis that pressure-induced intrinsic arterial tone is regulated differently in neonatal and adult cerebral arteries. In cannulated and pressurized endothelium-intact mouse cerebral arteries <150 µm in diameter, active intrinsic tone was evident at intraluminal pressures as low as 10 mmHg in neonatal arteries, but only at pressures of 60 mmHg or greater in adult arteries. Administration of 10 µM indomethacin produced no significant effect on tone at any pressure in either neonatal or adult arteries, but subsequent addition of 100 µM nitroarginine methyl ester (NAME) significantly vasoconstricted both neonatal and adult arteries at all pressures. Conversely, administration of 100 µM NAME alone significantly vasoconstricted adult arteries only, and subsequent addition of 10 µM indomethacin produced a significant additional vasoconstriction in adult arteries only, indicating an important interaction between the nitric oxide synthase and cyclooxygenase pathways, at least in adult arteries. In the presence of both indomethacin and NAME, intrinsic tone was significantly greater in neonatal than adult arteries, but when the endothelium was removed, tone was similar in neonatal and adult arteries at all pressures. Together, these results suggest that pressure-induced myogenic tone is regulated similarly in neonatal and adult mouse cerebral arteries but that the contribution of endothelial vasoactive factors to intrinsic tone is highly age dependent.

neonatal mouse; myogenic tone; pressure; cerebral artery


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