Regression of atherosclerosis: role of nitric oxide and apoptosis.

TLDR: Results indicate that supplemental L-arginine induces apoptosis of macrophages in intimal lesions by its metabolism to NO, which acts through a cGMP-independent pathway, consistent with previous observation that supplementation of dietary arginine induces regression of atheroma in this animal model.

Abstract: Background—We have recently found that administration of l-arginine to hypercholesterolemic rabbits induces regression of preexisting lesions. Others have previously shown that activation of the l-arginine/nitric oxide (NO) synthase pathway can induce apoptosis of vascular cells in vitro. Accordingly, the current study was designed to determine if dietary supplementation of l-arginine induces apoptosis of intimal lesions and if this effect is mediated through the NO synthase pathway. Methods and Results—Male New Zealand White rabbits were fed a 0.5% cholesterol diet for 10 weeks and subsequently placed on 2.5% l-arginine HCl in the drinking water, and the cholesterol diet was continued for 2 weeks, at which time the aortas were harvested for histological studies. l-Arginine treatment increased the number of apoptotic cells (largely macrophages) in the intimal lesions by 3-fold (11.9±3.9 vs 3.9±1.4 apoptotic cells/mm2, P<0.01). In subsequent studies, aortas were harvested for ex vivo studies. Aortic segmen...