Dose dependent protective effects of resveratrol treatment on hypercholesterolemic rabbit corpus cavernosum tissue

Impaired release and reduced bioavailability of nitric oxide are the hallmark for endothelial as well as erectile dysfunction. Hypercholesterolemia is known to be a risk for endothelial dysfunction that results in vasculogenic erectile dysfunction. Our aim was to investigate whether treatment with resveratrol have potential to protect corpora cavernosa (CC) of the penis from the affect of hypercholesterolemia.Adult male New Zealand rabbits were divided into three groups as; control (Group 1, n=7), cholesterol-fed animals (Group 2, n=7), and cholesterol-fed with 8mg/kg/day resveratrol treatment (Group 3, n=7). In the first step of the study animals were treated with 4 mg/kg/day, 6 mg/kg/day and 8 mg/kg/day dose of resveratrol. 8mg/kg/day resveratrol treatment proved Ach-mediated relaxation responses significantly higher than the other dose treatments. All animals except control were fed with 2% a/a cholesterol diet for 6 weeks. Resveratrol was administered with drinking water for 6 weeks. Total cholesterol, HDL and LDL levels were measured in all animals at the beginning and at the end of the study. Endothelial functions in CC was assessed by isolated tissue bath with cumulative doses of acetylcholine (Ach) (10-8 -10-5 M) in the presence and absence of L-nitro-N-Arginin metilester (LNAME).Feeding rabbits with cholesterol-diet for 6 weeks resulted in hypercholesterolemia confirmed by blood measurements. Resveratrol administration to the cholesterol-fed animals for 6 weeks did not restore increased blood cholesterol levels. While Ach-induced relaxation responses were significantly reduced in group-2 compared to control (%29,09±3,95 vs %48,58±4,16, p<0.01), resveratrol administration augmented these responses dose dependently(4 mg %44,7% ± 7,25, 6mg % 51.7 ±10.88 and 8mg %53,01±3.88).This study has demonstrated that resveratrol administration in hypercholesterolemia-induced rabbits for 6 weeks could dose-dependently protect corpora cavernosal smooth muscle relaxation of the penis without affecting blood lipid levels, resulting in preserved endothelial and erectile function.