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Figure 1. Potential mechanisms by which aging impairs vascular function
(A) and oral L-CIT may improve age-related vascular dysfunction (B). L-ARG is catabolized by the enzyme arginase into urea and L-ornithine (1). Age-related increased NADPH oxidase (NOx) activity increases superoxide anion (O2 −) production (2) and contributes to decrease BH4, leading to eNOS uncoupling (3). Uncoupled eNOS produces O2 −, which reacts with NO to produce peroxynitrite (ONOO−) (3), a substance that causes oxidative cell damage. The resultant low NO fails to properly activate the guanylate cyclase (GC)–GTP–cGMP signal transduction pathway, leading to impaired vasodilation (4). L-Ornithine produced by arginase increases the production of polyamine and proline, resulting in collagen synthesis and cell proliferation contributing to arterial stiffness (5). Oral L-CIT supplementation increases L-ARG bioavailability for eNOS by greater de novo synthesis (6) and inhibition of arginase activity (7), resulting in improved NO-mediated vasodilation (8) and decreased arterial stiffness (9). The precise mechanism by which L-CIT may decrease arterial stiffness is yet unknown.
