Impact of Hypertension, Aging, and Antihypertensive Treatment on the Morphology of the Pudendal Artery

Abstract

Aging and hypertension increase the risk of erectile dysfunction (ED) and cardiovascular disease. Arterial insufficiency is likely a primary factor in hypertension-related ED. Given the dominance of internal pudendal arteries in controlling penile vascular resistance, pathological changes in this vessel would be critical for inducing ED in aged hypertensives. We assessed the age-related impact of hypertension and its treatment on erectile function and pudendal artery structure in young and old spontaneously hypertensive rats (SHRs). Erectile responses were monitored in 15- and 77-week-old SHR and Wistar Kyoto (WKY) rats using apomorphine (80 mg/kg). At sacrifice, the vasculature was perfusion-fixed and aorta, renal, mesenteric, and internal pudendal arteries assessed morphometrically using light and electron microscopy. A separate group of 15-week SHR were treated with enalapril and hydrochlorothiazide (30 mg/kg/day, 2 weeks) followed by 2 weeks off treatment, after which the same vessels were assessed morphometrically. Arterial pressures were determined using radiotelemetry. Erectile function, vessel morphology (lumen diameter, wall thickness, cross-sectional area, extracellular matrix [ECM]) and arterial pressure. Erectile responses were similar in young SHR and WKY (1.7 ± 0.80 vs. 1.4 ± 0.85) but declined significantly in aged SHR (0.3 ± 0.49). Vascular aging in SHR was associated with striking pudendal remodeling, characterized by marked neointimal proliferation and disruptions of the internal elastic lamina. This remodeling involved thickening of the medial layer (35 ± 6.0 µm vs. 81 ± 3.5 µm, P < 0.01), decreased lumen diameter (282 ± 6.3 µm vs. 250 ± 12.4 µm, P < 0.05) and increased ECM (10 ± 2.0 µm² vs. 26 ± 10.6 µm², P < 0.001). In old pudendals, there were significantly more round synthetic smooth muscle cells bordering the intima and in the neointima. Antihypertensive treatment decreased the wall:lumen ratio in young SHR pudendal arteries (-17%). Vascular aging in SHR with ED involved distinctive pathogenic remodeling in the internal pudendal artery. In young SHR, brief antihypertensive therapy was able to regress this abnormal morphology.