Abstract
Inflammation and endothelial dysfunction play important roles in hypertension, disease associated with erectile dysfunction (ED). Growing evidence suggests that the immune system through activation of toll-like receptors (TLRs), such as TLR4, may contribute to this process. We hypothesized that chronic treatment with anti-TLR4 antibody improves erectile function in DOCA-salt hypertensive rats. Sprague-Dawley normotensive rats (Sham) and DOCA-salt (deoxycorticosterone acetate 200mg/kg, 6 weeks) hypertensive rats were treated with antibody anti-TLR4 (1ug/day, i.p.) or vehicle in the last 3 weeks. Erectile function was evaluated in vivo through measurements of changes in intracavernosal pressure/mean arterial pressure ratio (ICP/MAP) during electrical stimulation (EFS) of the major pelvic ganglion (MPG). Functional responses of cavernosal tissue were also performed. Anti-TLR4 treatment improved erectile function and significantly lowered blood pressure in DOCA-salt rats (Fig. *p<0.05 DOCA treated vs. untreated). DOCA-salt rats exhibited increased maximal contractile response to phenylephrine (1.53±0.2 vs. 0.92±0.12mN) and EFS (1.36±0.14 vs. 0.88±0.11mN, respectively) compared to Sham, which was attenuated (20±1.3% to PE and 26.5±2% to EFS) by anti-TLR4 treatment. Furthermore, this treatment enhanced nitrergic relaxation (16Hz) in penile tissue from DOCA-salt rats (33±3% untreated vs. 52±4% treated, p<0.05). In conclusion, these results suggest that TLR4 may mediate hypertension-associated ED.
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