Impaired renal vascular endothelial function in vitro in experimental hypercholesterolemia

Hypercholesterolemia (HC) induces alterations in systemic vascular reactivi ty, which can manifest as an attenuated endothelium-dependent relaxation, p artly consequent to an impairment in nitric oxide (NO) activity. To determi ne whether experimental HC has a similar effect on renal vascular function, renal artery segments obtained from pigs fed a HC (n = 5) or normal (n = 5 ) diet were studied in vitro. Endothelium-dependent relaxation was examined using increasing concentrations of acetylcholine (Ach), calcium ionophore A23187, and Ach following pre-incubation with N-G-monomethyl-L-arginine or L-arginine (L-ARG). The NO-donor diethylamine (DEA) was used to examine smo oth muscle relaxation response and cyclic GMP generation in endothelium-den uded vessels. The expression of endothelial NO synthase (eNOS) in the renal arteries was examined using Western blotting. Endothelium-dependent relaxa tion to Ach was significantly attenuated in the HC group compared to normal (53.3 +/- 9.1 vs. 98.8 +/- 3.7%, P < 0.005), but normalized after pre-incu bation with L-ARG (82.3 <plus/minus> 13.8%, P = 0.21). Receptor-independent endothelium-dependent relaxation to A23187 was also significantly blunted in HC (75.2 +/- 10.5 vs. 115.5 +/- 4.2%, P < 0.017). Smooth muscle relaxati on and cyclic GMP generation in response to DEA were greater in denuded HC vessels, while relaxation of intact vessels to nitroprusside was unaltered. In the HC vessels eNOS was almost undetectable. In conclusion, experimenta l HC attenuates in vitro endothelium-dependent relaxation of the porcine re nal artery, possibly due to low bioavailability of NO. These vascular alter ations in HC could play a role in the pathogenesis of renal disease or hype rtension, supporting a role for HC as a risk factor for renovascular diseas e. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.