期刊
JOURNAL OF APPLIED PHYSIOLOGY
卷 102, 期 1, 页码 63-71出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/japplphysiol.00660.2006
关键词
endothelium-dependent vasodilation; dimethylarginine dimethylaminohydrolase II; L-arginine paradox
资金
- NCRR NIH HHS [5-01-RR-00051] Funding Source: Medline
- NIA NIH HHS [AG-19365, AG-00847, AG-13038] Funding Source: Medline
- NATIONAL INSTITUTE ON AGING [R01AG013038, R21AG019365, R37AG013038] Funding Source: NIH RePORTER
Aging is associated with a decline in vascular endothelial function, manifesting in part as impaired flow- mediated arterial dilation ( FMD), but the underlying mechanisms are uncertain. Impaired FMD may be mediated in part by a decrease in synthesis of nitric oxide by endothelial nitric oxide synthase, and in clinical populations this has been attributed to competitive inhibition of L-arginine binding sites by asymmetric dimethylarginine ( ADMA). If this mechanism is involved in the age- associated decline in FMD, increasing L-arginine concentration may swing the competitive balance in favor of L-arginine binding, restoring nitric oxide synthesis, and enhancing FMD in older humans. To test this hypothesis, we measured FMD ( brachial ultrasound) in 10 younger ( 21 +/- 1 yr) and 12 older healthy men and women ( 60 +/- 2 yr) following infusion of vehicle or vehicle + L-arginine. Baseline FMD in the older subjects was only similar to 60% of that in the younger subjects ( P = 0.002). L-Arginine did not significantly increase FMD in either group despite 23-fold ( older) and 19-fold ( younger) increases in plasma L-arginine concentrations ( P < 0.0001 vs. control). Protein expression ( immunofluorescence) in vascular endothelial cells showed that ADMA and the enzyme isoform that controls its degradation, dimethylarginine dimethylaminohydrolase II, were not different in the younger and older subjects. Endothelium-independent vasodilation ( sublingual nitroglycerine) was not different between age groups or conditions. We conclude that acutely increasing plasma concentrations of L- arginine do not significantly improve brachial artery FMD in healthy older subjects and thus does not restore the age- associated loss of FMD. Together with the finding that endothelial cell ADMA protein expression was not increased in older adults, these findings suggest that competitive inhibition of L- arginine binding sites on endothelial nitric oxide synthase by ADMA is not an important mechanism contributing to impaired conduit artery endotheliumdependent dilation with aging in healthy humans.
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