1: FASEB J. 2000 Sep;14(12):1775-83. 

Physiological cyclic stretch directs L-arginine transport and metabolism to
collagen synthesis in vascular smooth muscle.

Durante W, Liao L, Reyna SV, Peyton KJ, Schafer AI.

Houston VA Medical Center and the Departments of Medicine. Pharmacology, Baylor
College of Medicine, Houston, Texas 77030, USA. wdurante@bcm.tmc.edu

Application of cyclic stretch (10% at 1 hertz) to vascular smooth muscle cells
(SMC) increased L-arginine uptake and this was associated with a specific
increase in cationic amino acid transporter-2 (CAT-2) mRNA. In addition, cyclic
stretch stimulated L-arginine metabolism by inducing arginase I mRNA and
arginase activity. In contrast, cyclic stretch inhibited the catabolism of
L-arginine to nitric oxide (NO) by blocking inducible NO synthase expression.
Exposure of SMC to cyclic stretch markedly increased the capacity of SMC to
generate L-proline from L-arginine while inhibiting the formation of polyamines.
The stretch-mediated increase in L-proline production was reversed by
methyl-L-arginine, a competitive inhibitor of L-arginine transport, by
hydroxy-L-arginine, an arginase inhibitor, or by the ornithine aminotransferase
inhibitor L-canaline. Finally, cyclic stretch stimulated collagen synthesis and
the accumulation of type I collagen, which was inhibited by L-canaline. These
results demonstrate that cyclic stretch coordinately stimulates L-proline
synthesis by regulating the genes that modulate the transport and metabolism of
L-arginine. In addition, they show that stretch-stimulated collagen production
is dependent on L-proline formation. The ability of hemodynamic forces to
up-regulate L-arginine transport and direct its metabolism to L-proline may play
an important role in stabilizing vascular lesions by promoting SMC collagen
synthesis.

PMID: 10973927 [PubMed - indexed for MEDLINE]