EXPERIMENTAL HYPERCHOLESTEROLEMIA IN RABBITS INDUCES CAVERNOSAL ATHEROSCLEROSIS WITH ENDOTHELIAL AND SMOOTH-MUSCLE CELL DYSFUNCTION

Hypercholesterolemia and other vascular risk factors for atheroscleros is are commonly associated with impotence. To characterize cavernosal smooth muscle reactivity in hypercholesterolemia, we performed isometr ic tension studies (with norepinephrine, acetylcholine, papaverine and electrical field stimulation) on isolated strips of corpus cavernosum from rabbits fed a 1% cholesterol diet. To assess the impact of chole sterol reduction, a group of rabbits was fed a cholesterol diet for 4 weeks and was then returned to a normal diet for 4 weeks before testin g. Potential structure-function relationships were delineated by ultra structural evaluation with transmission electron microscopy (TEM). All forms of cavernosal relaxation, including papaverine relaxation, were impaired with hypercholesterolemia, and norepinephrine contraction wa s augmented. In addition, ultrastructural evidence of an early atheros clerotic process in the cavernosal sinusoids was detected. Importantly , reduction of elevated serum cholesterol normalized cavernosal relaxa tion, including that of papaverine, and decreased the sensitivity to n orepinephrine, thereby suggesting that cavernosal smooth muscle dysfun ction in hypercholesterolemia is reversible.