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This Article Full Text Full Text (PDF) All Versions of this Article: 289/5/H2220    most recent 01013.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by White, C. R. Articles by Pearce, W. J. Search for Related Content PubMed PubMed Citation Articles by White, C. R. Articles by Pearce, W. J.

Maturation enhances fluid shear-induced activation of eNOS in perfused ovine carotid arteries

¹Center for Perinatal Biology, Loma Linda University, Loma Linda; and ²La Jolla Bioengineering Institute, La Jolla, California

Submitted 4 October 2004 ; accepted in final form 26 May 2005

The present study tests the hypothesis that age-dependent increases in endothelial vasodilator capacity are due to maturational increases in endothelial nitric oxide (NO) synthesis and release. Intact 4-cm carotid artery segments taken from term fetal lambs and nonpregnant adult sheep were perfused by using a closed system that enabled independent control of flow and inflow pressure and facilitated complete recovery of all NO released. Fluid shear stress induced a graded release of NO (in nmol NO·min·cm^–2 of luminal surface area) that was significantly greater in adult (890 ± 140) than in fetal (300 ± 40) carotid arteries at corresponding values of shear stress (5.9 ± 0.3 dyn/cm²) but was independent of inflow pressure in both age groups. These age-related differences in NO release were not attributable to corresponding differences in endothelial NO synthase (eNOS) abundance, as eNOS protein levels (in ng of eNOS/cm² of luminal surface area) were similar in adult (14 ± 2) and fetal (12 ± 1) arteries. Adult (80 ± 15) and fetal (89 ± 32) levels of eNOS mRNA (in 10⁶ copies/cm² of luminal surface area) were also similar. However, when NO release was normalized relative to the associated mass of eNOS protein to estimate eNOS-specific activity in situ, this value (in nmol NO·µg of eNOS^–1·min^–1) was significantly greater in adult (177 ± 44) than in fetal (97 ± 36) arteries when the endothelium was maximally activated by A-23187. Similarly, the slope of the relation between fluid shear stress and estimated eNOS-specific activity (in nmol NO·µg of eNOS^–1·min^–1 per dyn/cm²) was also significantly greater in adult (6.8 ± 0.1) than in fetal (2.9 ± 0.1) arteries, which suggests that eNOS may be more sensitive to or more efficiently coupled to activating stimuli in adult compared with fetal arteries. We conclude that maturational increases in endothelial vasodilator capacity are attributable to age-dependent increases in NO release secondary to elevated eNOS-specific activity and involve more efficient coupling between endothelial activation and enhancement of eNOS activity in adult compared with fetal arteries.

endothelium; endothelial nitric oxide synthase; postnatal; vasodilation; cardiovascular regulation

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