Calcification of the Internal Pudendal Artery and Development of Erectile Dysfunction in Adenine-Induced Chronic Kidney Disease: A Sentinel of Systemic Vascular Changes

Abstract

Introduction Chronic kidney disease (CKD), erectile dysfunction (ED), and cardiovascular disease share common vascular etiologies and risk factors. Aim Using a rat model, this is the first study to characterize the consequences of CKD in the onset and development of ED associated with differential regional vascular calcification and circulatory changes. Methods Stable CKD was generated at 3 weeks in male Sprague-Dawley rats given dietary adenine and progressed until 7 weeks. Mineral content and morphometry were assessed in the internal pudendal arteries (IPAs), thoracic aorta, and carotid artery. Endothelial function was determined via changes in serum von Willebrand factor (VWF) and endothelium-dependent relaxation of the thoracic aorta. Results In severe CKD rats, calcium and phosphate content in all arteries increased, and pulse wave velocity was elevated. Distal IPA segments, in particular, were the first to calcify, but penile tissue per se did not. CKD rats had endothelial dysfunction, as indicated by a decrease in acetylcholine-mediated relaxation (∼40%) and an increase in serum VWF (∼40%), as well as increased lumen diameter (20%) of the distal IPA. Erectile function, assessed using a centrally acting dopaminergic agent, was significantly impaired by 7 weeks (∼40%). Conclusions In CKD, the distal IPA appears to be more susceptible to vascular dysfunction and calcification. Additionally, the onset of ED may be an important sentinel of impending systemic vascular disease. To confirm this concept, future experimental and clinical studies will need to examine a range of vessel types and the use of supplementary methods to assess erectile function.

Enhanced Electrical Field Stimulated Nitrergic and Purinergic Vasoreactivity in Distal vs Proximal Internal Pudendal Arteries

“…The distal IPA have been shown to have an increased wall thickness and decreased lumen diameter compared to the proximal IPA indicating that distal IPA exhibit greater vascular resistance [7] . Despite an increased medial smooth muscle layer, no notable differences in KCl or PE induced contractions were observed between proximal or distal IPA suggesting that ion channel and adrenergic receptor populations are similar.…”

“…Despite an increased medial smooth muscle layer, no notable differences in KCl or PE induced contractions were observed between proximal or distal IPA suggesting that ion channel and adrenergic receptor populations are similar. Increased vascular resistance correlates with an increase in shear stress, a known contributor to endothelial damage leading to vascular remodeling of smooth muscle in disease states such as hypertension, diabetes, and chronic kidney disease [2,7,8,16] . Interestingly, in rats with chronic kidney disease, the distal IPA demonstrated greater smooth muscle remodeling and calcification that was otherwise absent in the proximal IPA or the penis [7] .…”

“…In humans and in the rat, the IPA originates from the internal iliac artery, runs along the lateral wall of the pelvis and terminates by branching into the dorsal and deep arteries of the penis [6] . We and others have defined the proximal IPA as the segment from the internal iliac to the gluteal artery branch and the distal portion is from the gluteal artery to the bifurcation of the dorsal and deep penile arteries [6,7] . Pathologic vascular remodeling in the distal IPA has been observed in rat models of aging, hypertension, and chronic kidney disease which also demonstrate ED [6–8] .…”

“…Pathologic vascular remodeling in the distal IPA has been observed in rat models of aging, hypertension, and chronic kidney disease which also demonstrate ED [6–8] . Maio and colleagues revealed extensive arterial wall calcification in the distal IPA from chronic kidney disease rats that was absent in the proximal IPA [7] . The cause of the disproportionate pathological remodeling between the proximal and distal segments of the IPA is unknown.…”

“…The cause of the disproportionate pathological remodeling between the proximal and distal segments of the IPA is unknown. Distal IPA have been shown to have a thicker smooth muscle layer and a smaller lumen diameter compared to proximal IPA in rats [7] . To our knowledge, the differences in vasoreactivity between the proximal and distal IPA have not been examined.…”