α 1 ‐Adrenoceptors are required for normal male sexual function

Background and purpose: α 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 α 1A ‐adrenoceptors compared with other drugs of this class. This suggests that α 1A ‐adrenoceptors may contribute to ejaculation. However, this has not been studied at the molecular level. Experimental approach: The physiological contribution of each α 1 ‐adrenoceptor subtype was characterized using α 1 ‐adrenoceptor subtype‐selective knockout (KO) mice ( α 1A ‐, α 1B ‐ and α 1D ‐AR KO mice) since the subtype‐specific drugs available are only moderately selective. We analysed the role of α 1 ‐adrenoceptors in the blood pressure and vascular response as well as ejaculation by determining these variables in α 1 ‐adrenoceptor subtype‐selective KO mice and in mice with all their α 1 ‐adrenoceptor subtypes deleted ( α 1 ‐AR triple‐KO mice). Key results: The pregnancy rate was reduced by 50% in α 1A ‐adrenoceptor KO mice, and this reduction was dramatically enhanced in α 1 ‐adrenoceptor triple‐KO mice. Contractile tension of the vas deferens in response to noradrenaline was markedly decreased in α 1A ‐adrenoceptor KO mice, and this contraction was completely abolished in α 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 α 1 ‐adrenoceptors, particularly α 1A ‐adrenoceptors, are required for normal contractility of the vas deferens and consequent sperm ejaculation as well as having a function in fertility. British Journal of Pharmacology (2007) 152 , 332–340; doi: 10.1038/sj.bjp.0707366 ; published online 2 July 2007