Yohimbine relaxes the human corpus cavernosum through a non-adrenergic mechanism involving the activation of K+ATP-dependent channels

Abstract

The mechanism by which yohimbine relaxes the human corpus cavernosum remains unclear. Using the human corpus cavernosum strips immersed in isometric baths containing Krebs-Henseleit solution, this study investigates the effect of yohimbine on the relaxation of the human corpus cavernosum through nitrergic pathways involving the activation of ATP-dependent potassium channels (K ATP ). The maximal relaxation induced by yohimbine in the human corpus cavernosum strips pre-contracted with phenylephrine was 100±0% and only 30.5±5.0% when they were precontracted with 60-mM potassium (K þ ) solution. The maximal relaxation induced by yohimbine in phenylephrine pre-contracted tissues was significantly inhibited by tetrodotoxin, 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or 7-nitroindazole (43.6, 36.1 and 42.6%, respectively). Neither the combination charybdotoxin-apamin nor tetraethylammonium altered the response of the human corpora cavernosa strips to yohimbine. Nevertheless, glibenclamide decreased the maximum relaxant response to yohimbine by 29.8% (Po0.05; n ¼ 12). The results suggest that yohimbine relaxes the human corpus cavernosum by a non-adrenergic, non-cholinergic mechanism, probably activating the nitrergic-soluble guanylate cyclase (NO-sGc) pathway and K ATP .

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

“…Several studies have documented that K channel modulators, putative activators of the K ATP channel, elicit a concentrationdependent relaxation of isolated human corporal smooth muscle (Andersson, 1992. Although activation of the K ATP channel has been suggested to be involved in the action of yohimbine (Freitas et al, 2009), phentolamine (Silva et al, 2005) and testosterone (Yildiz et al, 2009) on cavernosal tissue, the importance of this contribution to the total effects of these agents on erectile mechanisms has not been established.…”

Aspidosperma excelsum and its pharmacological potential: in silico studies of pharmacokinetic prediction, toxicological and biological activity

“…Furthermore, it is already known yohimbine acts directly in blocking α-1-adrenergic receptors, decreasing the synthesis of IP3 and releasing Ca 2+ causing muscle relaxation (Hodges & Sparks, 2013). Studies also suggest that yohimbine acts in the muscle relaxation of human cavernous tissue by nonadrenergic pathway, probably activating the nitrergic soluble guanylate cyclase (NO-SGC) via and KATP (Freitas, et al, 2009).…”

Short-term diabetes decreases ischemia reperfusion-induced arrhythmia: the effect of alpha-2 blocker yohimbine and glibenclamide

“…Sulfonylurea drugs are commonly used to treat diabetes. However, these drugs also increase erectile dysfunction (Freitas et al, 2009). No epidemic research was found on whether the incidence of erectile dysfunction increases in patients using glibenclamide.…”