Vasoconstrictors in erectile physiology.
The erectile response of the penis depends on a balance between vasoconstrictor agents which cause cavernosal smooth muscle to contract limiting blood inflow, and vasodilators which relax cavernosal smooth muscle leading to increased blood inflow and erection. This review emphasizes the role of vasoconstrictors in the penis and shows that both endothelin-1 (ET-1) and the alpha-adrenergic agonist, methoxamine (METHOX) exert strong vasoconstrictor actions in the cavernosal circulation. We recently reported the vasoconstrictor actions of exogenous ET-1 and METHOX to be mediated by the RhoA/Rho-kinase pathway in the cavernosal circulation. While it is widely held that the nitric oxide-cyclic GMP-protein kinase G (NO-cGMP-PKG) pathway mediates vasorelaxation and penile erection, the interaction between this pathway and the vasoconstrictor process remains to be fully elucidated. Our studies also have shown that, during erection, the vasoconstrictor action of METHOX and ET-1 are inhibited and that NO is likely responsible for this inhibition. We hypothesize that the NO-cGMP-PKG pathway controls erection by acting in two distinct ways-by lowering intracellular levels of calcium leading to vasorelaxation and by inhibiting Rho-kinase mediated vasoconstriction.
Mills
T M
TM
Department of Physiology, Medical College of Georgia, Augusta, Georgia 30912-3000, USA. tmills@mail.mcg.edu
Chitaley
K
K
Lewis
R W
RW
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D019332:Endothelin-1 / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000502:physiology; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D019332:Endothelin-1; D047908:Intracellular Signaling Peptides and Proteins; D014662:Vasoconstrictor Agents; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D008729:Methoxamine