Effect of Rho-kinase inhibition on vasoconstriction in the penile circulation

• Published in: Journal of applied physiology (1985) Vol. 91; no. 3; pp. 1269 - 1273
• Main Authors: Mills, Thomas M, Chitaley, Kanchan, Wingard, Christopher J, Lewis, Ronald W, Webb, R. Clinton
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.09.2001; American Physiological Society
• Subjects: Amides - pharmacology; Animals; Biological and medical sciences; Blotting, Western; Circulatory system; Effects; Electric Stimulation; Endothelin-1 - pharmacology; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Intracellular Signaling Peptides and Proteins; Male; Males; Mammalian male genital system; Methoxamine - pharmacology; Morphology. Physiology; Penile Erection - drug effects; Penile Erection - physiology; Penis - blood supply; Penis - enzymology; Protein-Serine-Threonine Kinases - analysis; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Reproductive system; rho-Associated Kinases; Vasoconstriction - drug effects; Vasoconstriction - physiology; Vasoconstrictor Agents - pharmacology; Vertebrates: reproduction; Rat; Enzyme; Transferases; Rodentia; Vasoconstriction; Endothelin 1; Male genital system; Vasodilation; Vasomotricity; Vertebrata; Mammalia; Protein kinase; Penis; Inhibition
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/jappl.2001.91.3.1269

Department of Physiology and Urology Section, Department of Surgery, Medical College of Georgia, Augusta, Georgia 30912-3000 A recent report from this laboratory (Chitaley K, Wingard C, Webb R, Branam H, Stopper V, Lewis R, and Mills T.  Nature Medicine 7: 119-122, 2001) showed that inhibition of Rho-kinase increased the erectile response (intracavernosal pressure and mean arterial pressure) by a process that does not require nitric oxide or cGMP. The present study investigated whether vasoconstrictor agents, which are active in the penis, act via the Rho-kinase pathway. Western analysis revealed RhoA and Rho-kinase protein in the penis. Treatment with the selective Rho-kinase inhibitor Y-27632 significantly increased the magnitude of the erectile response. Intracavernous administration of endothelin-1 (ET-1; 50 pmol) or methoxamine (10 µg/kg) reduced the erectile response to autonomic stimulation. If Y-27632 was given before ET-1 or methoxamine, the vasoconstrictor effect was reduced, and intracavernosal pressure and mean arterial pressure remained elevated. However, when given after methoxamine, Y-27632 had a reduced vasodilatory effect, and Y-27632 had no vasodilatory effect when given after ET-1. These findings suggest that ET-1 and methoxamine increase Rho-kinase activity in the cavernous circulation and support the hypothesis that the vasoconstriction that maintains the penis in the nonerect state is mediated, in part, by the Rho-kinase pathway. penile erection; vasodilation; penis; methoxamine; endothelin-1