Abstract 353: Castration Impairs Rat Internal Pudendal Artery Reactivity And Structure

Abstract

Testosterone deficiency is strongly associated with erectile dysfunction (ED). Inadequate penile arterial flow is one of the major causes of ED. Considering that blood flow to the corpus cavernosum is derived from the internal pudendal arteries (IPA), we hypothesized that castration induces impairment of IPAs reactivity and structure, contributing to ED. Male Wistar rats were studied 30 days after castration (Cast). Functional and structural properties of rat IPA were determined in wire and pressure myograph systems, respectively. Castrated rats exhibited impaired erectile function, represented by decreased intracavernosal pressure/mean arterial pressure ratio [ICP/MAP (sham = 0.5 ± 0.1; castrated = 0.2 ± 0.1; 20 Hz. p <0.05)]. Castrated rats exhibited decreased phenylephrine (Phe)- [(% Kcl) Control: 175.4 ± 4.6 vs Cast: 134,9 ± 11; Emax] and electrical field stimulation (EFS)-induced contraction [(% Kcl) Control: 213,0 ± 7.1 vs Cast: 137 ± 6.1; 12Hz] and decreased acetylcholine (ACh)- (Control: 79.7 ± 2.2 vs Cast: 49.8 ± 2.8; Emax) and EFS-induced vasodilatation (Control: 54.6 ± 2.1 vs Cast: 35.5 ± 1.6; 12hz). IPAs from Cast rats exhibited decreased internal diameter [Control (μm): 499.9 ± 35.9 vs Cast: 413.0 ± 14.8; 60 mmHg], external diameter [Control (μm): 669.4 ± 40.1 vs Cast: 552.0 ± 30.0; 60 mmHg], thickness of the arterial wall [Control (μm): 81.2 ± 6.4 vs Cast: 55.8 ± 7.5; 80 mmHg] and cross-sectional area [Control (μm2): 157217 ± 12533 vs Cast: 116383 ± 12424; 30 mmHg]. Castration decreased nNOS expression (60%) and increased p38 (Thr180/Tyr182) phosphorylation (450%), as well as cleavage of caspase 3 (270%). In conclusion, testosterone deficiency is associated with impairment of IPA reactivity and structure and increased apoptosis signalling markers. Our findings suggest that hypogonadism may contribute to IPA dysfunction, which can leads to ED. Financial support: FAPESP and CNPq.