Abstract P287: Endothelial Dysfunction in Small Resistance Arteries of Patients with Severe Obesity: Role of Arginase

Abstract

Nitric oxide (NO) is produced by endothelial NO synthase (eNOS) using the aminoacid L-Arginine. Arginase (Arg) also uses L-Arginine as substrate, converting it in L-Ornitine and urea. An increased Arg activity causes a progressive L-Arginine depletion, which in turn determines a lower NO bioavailability. Studies in murine models of obesity identify Arg as a determinant of endothelial dysfunction. In this study, we evaluated whether Arg might play a role in determining the lower bioavailability of NO in small resistance arteries isolated from subcutaneous tissue of patients with severe obesity (Ob), split in age groups (younger than 30 aa, range 21-29, n=5; older than 30 aa, range 35-56, n=5) vs normoweight controls (Ctrl younger 30 years, range 20-29, n=5; older than 30 yrs, range 36-58, n=5). Each patient underwent a subcutaneous biopsy during a laparoscopic surgical procedure. Small arteries, isolated from periadvential fat, were evaluated on a pressurized micromyograph. Endothelium-dependent vasodilation (VD) was assessed by acetylcholine (Ach, 0,001-100μM). NO availability was assessed by repeating Ach with L-NAME (100μM). Ach was also infused in the presence of norNOHA (10μM, Arg inhibitor). In Ctrl, VD induced by Ach was inhibited by L-NAME and not modified by norNOHA. Ob younger exhibited a reduced VD induced by Ach vs Ctrl of the same age, a reduced inhibition by L-NAME, and a potentiating effect by norNOHA, which also normalized the inhibitory effect of L-NAME on Ach. In Ob older, VD induced by Ach was reduced vs Ob younger, resistant to L-NAME and not modified by norNOHA. In conclusions, in small arteries from younger Ob, the Arg inhibition improves endothelial function by increasing the NO availability, while in older Ob Arg does not seem to play any role in endothelial dysfunction.