Physiology of penile erection and pathophysiology of erectile dysfunction

Abstract

This article reviews the physiology of penile erection, the components of erectile function, and the pathophysiology of erectile dysfunction. The molecular and clinical under-standing of erectile function continues to gain ground at a particularly fast rate. Advances in gene discovery have aided greatly in working knowledge of smooth muscle relaxation/contraction pathways. The understanding of the nitric oxide pathway has aided not only in the molecular understanding of the tumescence but also greatly in the therapy of erectile dysfunction.

Figure 1

Molecular mechanism of penile smooth muscle contraction. Norepinephrine from sympathetic nerve endings and endothelins and PGF2a from the endothelium activate receptors on smooth muscle cells to initiate the cascade of reactions that eventually result in elevation of intracellular calcium concentrations and smooth muscle contraction. Protein kinase C is a regulatory component of the Ca2+-independent, sustained phase of agonist-induced contractile responses. (From Lue TF: Erectile dysfunction. N Engl J Med 2000;342:1802–1813. Copyright “ 2000 Massachusetts Medical Society. All rights reserved.)

Figure 2

RhoA/Rho kinase pathway: the calcium sensitization pathway.

Figure 3

Molecular mechanism of penile smooth muscle relaxation. The intracellular second messengers mediating smooth muscle relaxation, cAMP and cGMP, activate their specific protein kinases, which phosphorylate certain proteins to cause opening of potassium channels, closing of calcium channels, and sequestration of intracellular calcium by the endoplasmic reticulum. The resultant fall in intracellular calcium leads to smooth muscle relaxation. Sildenafil inhibits the action of PDE5 and thus increases the intracellular concentration of cGMP. Papaverine is a nonspecific phosphodiesterase inhibitor. eNOS, endothelial nitric oxide synthase. (From Lue TF: Erectile dysfunction. N Engl J Med 2000;342:1802--1813. Copyright “ 2000 Massachusetts Medical Society. All rights reserved.)