Molecular mechanisms for the regulation of penile smooth muscle contractility

Abstract

Relaxation of smooth muscle is viewed as a ‘resetting’ of contractile machinery and the resumption of a pre-contractile state is accomplished by lowering cytosolic Ca²⁺ and/or by decreasing the sensitivity of the contractile machinery to Ca²⁺. There are several mechanisms whereby cytosolic Ca²⁺ can be reduced and relaxation achieved but, in general, all pathways depend upon the accumulation of cyclic nucleotides cAMP and cGMP or on the activation of K⁺ channels resulting in hyperpolarization. Recently, activation of Na⁺/K⁺ ATPase by nitric oxide has been shown to be involved in the relaxation of trabecular smooth muscle. Since Na⁺/K⁺ ATPase is electrogenic, its stimulation would cause hyperpolarization and, in turn, would prevent the opening of voltage-dependent Ca²⁺ channels. This manuscript briefly reviews the molecular mechanisms affected by muscle relaxants and vasodilators in the treatment of erectile dysfunction.