α₁‐Adrenoceptors are required for normal male sexual function

Abstract

Background and purpose: a 1 -Adrenoceptor antagonists are extensively used in the treatment of hypertension and lower urinary tract symptoms associated with benign prostatic hyperplasia. Among the side effects, ejaculatory dysfunction occurs more frequently with drugs that are relatively selective for a 1A -adrenoceptors compared with other drugs of this class. This suggests that a 1A -adrenoceptors may contribute to ejaculation. However, this has not been studied at the molecular level. Experimental approach: The physiological contribution of each a 1 -adrenoceptor subtype was characterized using a 1 -adrenoceptor subtype-selective knockout (KO) mice (a 1A -, a 1B -and a 1D -AR KO mice) since the subtype-specific drugs available are only moderately selective. We analysed the role of a 1 -adrenoceptors in the blood pressure and vascular response as well as ejaculation by determining these variables in a 1 -adrenoceptor subtype-selective KO mice and in mice with all their a 1 -adrenoceptor subtypes deleted (a 1 -AR triple-KO mice). Key results: The pregnancy rate was reduced by 50% in a 1A -adrenoceptor KO mice, and this reduction was dramatically enhanced in a 1 -adrenoceptor triple-KO mice. Contractile tension of the vas deferens in response to noradrenaline was markedly decreased in a 1A -adrenoceptor KO mice, and this contraction was completely abolished in a 1 -adrenoceptor triple-KO mice. This attenuation of contractility was also observed in the electrically stimulated vas deferens. Conclusions and implications:These results demonstrate that a 1 -adrenoceptors, particularly a 1A -adrenoceptors, are required for normal contractility of the vas deferens and consequent sperm ejaculation as well as having a function in fertility.

α1‐Adrenoceptors and ejaculatory function

“…In conclusion, the present study by Sanbe et al (2007) demonstrates an important role of a 1 -adrenoceptors, particularly a 1A -adrenoceptors, in vas deferens function, and inhibition of these effects can lead to male infertility. These findings may represent the mechanistic correlate of the clinically observed abnormal ejaculation with some a 1 -adrenoceptor antagonists (van Dijk et al, 2006), but some inconsistencies between mouse and human data as well as alternative possibilities remain to be investigated.…”

Modulation of Adrenergic Responses of Human Vas Deferens by K+ Channel Inhibitors

“…Increasing adrenergic motor function of the vas deferens has been demonstrated to be successful on the treatment of idiopathic oligospermia induced by aperistaltic vas deferens. 29 Sambe et al, 30 have shown that ␣ 1A -adrenoceptors are required for normal contraction of the vas deferens and consequent sperm ejaculation. Therefore, the contractile dysfunction of the vas deferens induced by the loss of functioning ␣ 1A -adrenoceptors can explain the side effects observed in patients being treated with an ␣ 1A -adrenoceptor blocker by benign prostatic hyperplasia as well as prostatitis.…”

Role of Ca2+-activated K+ channels and Na+,K+-ATPase in prostaglandin E1- and E2-induced inhibition of the adrenergic response in human vas deferens

“…An important function of the vas deferens is the transport of spermatozoa from the epididymis for inclusion in the semen. Since a 1 -adrenoceptors activation by norepinephrine is required for normal contraction of the vas deferens and consequent sperm ejaculation [38], it seems likely that increased formation of PGE 2 in physiological and pathological conditions such as inflammation [39], may cause aperistalsis of the adrenergically innervated vas deferens by activating K Ca 1.1 channels and Na + ,K + -ATPase and impairment of male fertility. Although the present studies provide evidence that activation of presynaptic K Ca 1.1 channels inhibits adrenergic contractions of vas deferens, future studies are necessary to elucidate the potential therapeutic modification of vas deferens motility, via pharmacologic intervention of these channels.…”