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