Abstract
Abstract Introduction Diabetes mellitus (DM) is a chronic metabolic disease with epidemiological relevance worldwide. One of the most common and most underestimated complications of diabetes is erectile dysfunction (ED). It is estimated that approximately 35-90% of diabetic men present ED as an early complication. Previous studies have shown that TRPM8 activation triggers relaxation of pudendal artery with increased sensitivity in the hypertensive rats. However, despite the correlation between ED and diabetes, research on the role of TRPM8 channels in the vasculature responsible for sexual function in diabetic condition still needs to be elucidated. Objective In this way, the aim of this study was to investigate TRPM8 channels in arteries vital to erection of the penis. We hypothesized that TRPM8 activation would induce relaxation and reduce sensitivity to alpha-adrenergic stimulation in pudendal arteries from diabetic mice. Methods Male control and db/db mice were euthanized, and the internal pudendal arteries were mounted on DMT wire myographs for the measurement of isometric force. Results Cumulative administration of icilin (10-8 to 10-4M), a TRPM8 agonist, induced endothelium-dependent and endothelium-independent relaxation in pre-contracted rings with phenylephrine (Phe,1μM). Relaxant effect induced by icilin was similar between pudendal arteries from db/db (Emax: 56.31 +/− 1.90%, n=5) and control (Emax:46.57 +/− 4.45%, n=5) mice. Diabetes increased the contractility of the pudendal artery in response to phenylephrine in concentration of 3x10-6M (99.40 +/− 4.65%, n=4) compared to control (85.44 +/− 2.36%, n=4). Interestingly, pre-incubation with icilin (10-4M) decreased the potency of the contraction induced by phenylephrine (10-9 to 3x10-5M) compared to untreated rings in both diabetic (pD2: 6.39 +/− 0.07 vs 6.67 +/− 0.05, n=4) and control (pD2: 6.43 +/− 0.09 vs 6.82 +/− 0.05, n=4) animals. In the pudendal artery, diabetes decreased the sensitivity to acetylcholine compared to control (pD2: 7.17 +/− 0.06 vs 7.42 +/− 0.03, n=4). However, the relaxation induced by acetylcholine (10-9 to 3x10-5M) was not changed by pre-incubation with icilin. Conclusions Icilin is able to promote relaxation with the same magnitude in pudendal arteries from diabetic and control mice. Increased responses to phenylephrine in pudendal artery may contribute to the development of ED. In addition, pre-incubation with icilin reduced sensitivity to phenylephrine, suggesting that the icilin could be a helpful treatment for ED. Disclosure No
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