Time course of development of erectile dysfunction and coronary artery endothelial dysfunction in response to a western diet: influence of endothelial nitric oxide synthase uncoupling

Epidemiological evidence suggests that men experiencing cardiac events may have preexisting erectile dysfunction (ED). Male Sprague‐Dawley rats (n = 5/group) were fed a control or western diet for 4, 8, or 12 weeks. Erectile function was evaluated by calculating the area under the curve (AUC) of intracavernosal pressure/mean arterial pressure in response to electrical field stimulation of the major pelvic ganglion, and again following intracavernosal injection of 10 μM sepiapterin (SA). Coronary artery segments were mounted on a wire myograph, pre‐constricted with serotonin and endothelial function was evaluated by cumulative doses of acetylcholine (ACh) (0.001 – 10 μM), and repeated in one segment following incubation in 10 μM SA. Erectile function was attenuated at 8 and 12 weeks (C: 286 ± 52, 4w: 232 ± 35, 8w: 123 ± 49, 12w: 160 ± 59 (AUC); p = 0.004). SA had no effect on erectile function at C or 4w, but showed improvement at 8w (225 ± 99, p = 0.13) and 12w (211 ± 80, p = 0.24). The western diet increased the coronary ACh EC 50 at 12w (C: 0.20 ± 0.18, 4w: 0.25 ± 0.15, 8w: 0.50 ± 0.32, 12w: 0.84 ± 0.55 μM; p = 0.046). SA had no effect on C, 4w or 8w, but improved the EC 50 38% at 12w (1.37 ± 2.06 vs 0.85 ± 0.77 μM). ED was manifest prior to coronary dysfunction. There is a trend for improved erectile and coronary function in the dysfunctional state with SA, suggesting that eNOS uncoupling is a common contributor to dysfunction in these vascular beds.