Erectile dysfunction and cardiovascular disease share etiologies, and commonly coexist. One unifying concept is that the arterial insufficiency in hypertension is also the primary basis for blunted sexual responses. The objective of these studies was to characterize the age-related changes in the structure and function of the pudendal artery (the main resistance vessel) in young and old normotensive and hypertensive animals in relation to erectile function. In addition, we assessed the impact of antihypertensive treatments and lifestyle modifications, such as exercise and/or caloric restriction, on erectile responses and the structure and function of the pudendal artery. In 30 week old hypertensive rats or following re-challenges at 50 and 70 weeks, antihypertensive treatment (enalapril or hydralazine) did not prevent the age-related decline in erectile function. Experiments involving cross-over kidney transplantations between treated and untreated young hypertensive rats revealed that changes in penile vasculature and not the level of arterial pressure were important for normalizing erectile responses. In addition, intervention with exercise and caloric restriction showed that these treatments substantially improved erectile responses in normotensive and hypertensive rats. The pudendal artery in young normotensive rats was found to have a thick medial layer but a relatively small lumen. With age, the pudendal lumen didn’t change, but all components of the medial layer were markedly increased. Of interest, the smooth muscle cells within the pudendal medial layer became more disorganized with aging, although iii contractions were similar. In contrast, endothelium-dependent relaxation decreased with age. Young hypertensive rats also had an increased wall thickness, but not lumen diameter or extracellular matrix. Antihypertensive therapy significantly decreased the pudendal wall thickness. In aging hypertensive rats, the pudendal artery walls were even thicker, lumen decreased and extracellular matrix greatly enhanced compared to younger rats. In addition, there were numerous regions of intimal thickening associated with marked disruptions of the internal elastic lamina. Moreover, pudendal smooth muscle cells bordering the intima and in the neointima were round in shape, and electron microscopy confirmed their synthetic state. Taken together, these findings provide key evidence of the importance of the structure and function of the pudendal artery in facilitating erectile responses. / Thesis (Ph.D, Pharmacology & Toxicology) -- Queen's University, 2009-05-19 12:55:30.469

Cardiovascular disease (CVD) and erectile dysfunction (ED) have common etiologies, such as increased adiposity and chronic diseases. Incident ED is known to be a sentinel of CVD, providing a unique opportunity for early lifestyle interventions to attenuate the progression of disease. The internal pudendal artery (IPA) plays an important role in controlling resistance to penile blood flow and thereby erections. Although morphological and functional disturbances in the IPA have been associated with ED, few studies have characterized changes in the IPA as it relates to increased adiposity and chronic diseases (e.g., chronic kidney disease [CKD]). Finally, although both vascular calcification and ED have been shown to be prevalent in patients with CKD, there has yet to be an assessment of associated mechanisms. The effect of lifestyle modifications on erectile function was evaluated in both experimental and clinical settings. Specifically, the studies assessed the effect of caloric restriction (CR) in rats and of chronic exercise in sedentary, overweight or obese male and female subjects. In rats, structural and functional changes of the IPA and erectile responses were characterized in relation to increasing adiposity and to CKD. Experimentally, the susceptibility of various vascular beds to calcification in CKD was determined. Clinically, erectile and female sexual function was assessed in patients with Stage 3 to 5 CKD, who had no history of CVD. In rats, CR blunted the accumulation of abdominal adiposity, and attenuated progression of both endothelial dysfunction and ED, independently of morphological changes in the IPA. Rats with CKD had an increased frequency of ED, greater endothelial dysfunction, and altered vascular morphology, yet vascular calcification per se did not account for ED. In the clinical study, sedentary and overweight or obese males with ED, but not females, had a significantly higher body mass index (BMI) and waist circumference. Chronic exercise significantly improved ED and female sexual dysfunction (FSD). Clinically, CKD was associated with ED and FSD as well as increased coronary artery calcification and endothelial dysfunction. These findings support the concept that early detection of cardiovascular abnormalities, using incident ED as a sentinel, should facilitate early interventions in otherwise asymptomatic populations. / Thesis (Ph.D, Pharmacology & Toxicology) -- Queen's University, 2013-09-30 22:33:20.436

La dysfonction érectile est l’un des types de dysfonctionnement sexuel aussi complexe chez les hommes que les femmes. Elle implique un facteur venogénique, artériogénique et de neurogénique. L'étiologie des changements de la puissance sexuelle après la prostatectomie radicale ainsi que la chirurgie vasculaire ou la radiothérapie des organes pelviens est probablement multifactorielle, l'une de ces causes est la blessure de l’artère destinée pénienne (mâle) et clitoridienne (femelle) lors d’une opération ou d’une radiothérapie. L’anatomie des artères destinées péniennes et clitoridiennes ainsi que ses origines sont variées. L’Angiographie par résornance magnétique (RM) et tomodensitométrie (TDM) nous donnent des images très nettes qui peuvent être utilisées avant l'intervention pour identifier et localiser les artères pudendales internes (API) et les artères pudendales accessoires (APA), et peuvent aider les chirurgiens et les radiothérapeutes à planifier une opération efficace visant à préserver l’API et l’APA, probablement importantes pour la fonction érectile après l’intervention sur les organes et les vaisseaux pelviens / Erectile dysfunction is one of the types of sexual dysfunction, the etiology is complex in male and female. It involves venogenic factor, arteriogenic and neural origins. The aetiology of changes in sexual potency after radical prostatectomy and pelvic vascular surgery or pelvic radiotherapy is probably multifactorial, one of these cause is injury the penile artery (male) and clitoris artery (female) during the operation or radiotherapy. The anatomy of the penile and clitoral artery is variation. Magnetic resonance (MR) and Multiple detector computed tomography (MDCT) angiography give us a very sharp image, they can be pre-intervation used to identify and localize internal pudendal artery (IPA) and accessory pudendal artery (APA), and may help surgeons and radiotherapists plan an effective intervation that preserves IPA and APA possibly important for sexual function after surgery or radiotherapy of the pelvic organs