Piezo1 Mechanosensor is Impaired in Pudendal Artery and Corpus Cavernosum of Spontaneously Hypertensive Rats

Abstract

Erectile dysfunction (ED) is highly associated with risk factors for cardiovascular diseases, including obesity, diabetes and arterial hypertension. The cavernous arteries respond to shear‐stress flow mediated vasodilation and this response is decreased in patients with either neurogenic and vasculogenic ED. Piezo1 channel is a non‐selective stretch‐activated ion channel which has been described to be expressed in the vasculature and it senses shear stress. Piezo1 channel has been shown to induce endothelial nitric oxide synthase activation to induce vasodilation whereas Piezo1 deficiency contributes to the development of arterial remodeling in hypertension. We hypothesize that in physiological conditions, upon sexual stimulation, increased blood flow mediates shear stress activating Piezo1 channels in the pudendal artery and corpus cavernosum, which facilitates relaxation of the arteries and the cavernous smooth muscle. On the other hand, in arterial hypertension the increased pressure causes decreased sensitivity of Piezo1 channel leading to decreased relaxation of the pudendal artery and corpus cavernosum, contributing to the development of erectile dysfunction. Corpus cavernosum and pudendal artery from male Wistar and spontaneously hypertensive rats [SHR (11 month‐old)] were removed, cleaned and mounted in wire myographs. Concentration response‐curves to Yoda1 (chemical agonist for Piezo1 channel) were performed in corpus cavernosum and pudendal artery in the presence or absence of nitric oxide synthase (NOS) inhibitor (L‐NAME, 100 μM, 30 min). Yoda1 causes concentration dependent relaxation in the corpus cavernosum and pudendal artery, which were significantly lower for SHR animals [Emax 14.80 ± 6.47 vs. 37.32 ± 2.10] (corpus cavernosum)] and [Emax 47.34 ± 7.59 vs. 25.52 ± 6.43 (pudendal artery)]. Further, acute NOS inhibition impairs corpus cavernosum relaxation to Yoda 1. In conclusion, thise results are very innovative since the concept that mechansensitive channels are expressed in the cavernous tissue and pudendal artery and may play a role for the erectile function has not been previously investigated. The data provided by this research will help to elucidate additional mechanisms related to ED and could bring new insight about therapeutic targets for the treatment of refractory ED.Support or Funding InformationNIH ‐ HL13604