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

Abstract

Introduction 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. Aim 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). Methods 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. Main Outcomes Measured Erectile function, vessel morphology (lumen diameter, wall thickness, cross-sectional area, extracellular matrix [ECM]) and arterial pressure. Results 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%). Conclusions 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.

Role of Adenosine Receptor(s) in the Control of Vascular Tone in the Mouse Pudendal Artery

“…Recent studies have shown that the PA contributes approximately 70% of total pudendal-penile vascular resistance, whereas the intrapenile vasculature contributes less than 25% of total resistance in this bed (Manabe et al, 2000). In addition, it has been demonstrated that optimal erection requires vasodilation of both prepenile arteries, such as the PA, as well as intrapenile arteries (Manabe et al, 2000;Hale et al, 2009;Hannan et al, 2011). To date, no studies have characterized the contribution of adenosine and its receptors in the regulation of the PA vascular tone.…”

Long-term effects of ACE inhibitor on vascular remodelling

“…However, the application of ACE inhibitor in hypertensive rats may be not as benefi cial in prevention of neointimal thickening as in normotensive ones [13]. Further, the effi cacy of such therapy may depend on age [14], way of application [15] and degree of atherosclerosis [16]. Unfortunately, some studies of primate or human tissues did not confi rm the benefi cial effects of this medication on the long-term changes of the vascular architecture [7,17].…”

Animal models of erectile dysfunction

“…Furthermore, a significant, but not strong, increase in collagen production was seen in 80-week-old Wistar rats (Lin, Tsai, Lin, Lin, & Chow, 2001), as were degeneration of the elastic fibers in 27-month-old Wistar rats (Calabro et al, 1996) and alterations in the cavernosal smooth muscle content and function in 24-to 30-month-old Wistar rats (Dahiya et al, 1999;Wespes, 2002). Hannan et al (2001) showed that erectile responses declined significantly in 77-week-old spontaneously hypertensive rats compared with 15-week-old spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKRs). Vascular aging in SHRs exhibited prominent remodeling with marked proliferation and disruption of internal elastic lamina (Hannan et al, 2001).…”

“…Hannan et al (2001) showed that erectile responses declined significantly in 77-week-old spontaneously hypertensive rats compared with 15-week-old spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKRs). Vascular aging in SHRs exhibited prominent remodeling with marked proliferation and disruption of internal elastic lamina (Hannan et al, 2001). In fact, studies have confirmed that SHRs average approximately 30% lower ICP than age-matched WKRs (Behr-Roussel et al, 2003).…”