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Effect of Rho-kinase inhibition on vasoconstriction in the penile circulation
- Source :
- Journal of Applied Physiology. 91:1269-1273
- Publication Year :
- 2001
- Publisher :
- American Physiological Society, 2001.
-
Abstract
- 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.
- Subjects :
- Male
medicine.medical_specialty
Pyridines
Physiology
Blotting, Western
Vasodilation
Protein Serine-Threonine Kinases
Methoxamine
Rho-Associated Kinases
Rats sprague dawley
Rats, Sprague-Dawley
Physiology (medical)
Internal medicine
medicine
Animals
Vasoconstrictor Agents
Enzyme Inhibitors
Protein kinase A
Rho-associated protein kinase
rho-Associated Kinases
Endothelin-1
business.industry
Penile Erection
Intracellular Signaling Peptides and Proteins
Amides
Endothelin 1
Electric Stimulation
Rats
Endocrinology
Vasoconstriction
medicine.symptom
business
Penis
medicine.drug
Subjects
Details
- ISSN :
- 15221601 and 87507587
- Volume :
- 91
- Database :
- OpenAIRE
- Journal :
- Journal of Applied Physiology
- Accession number :
- edsair.doi.dedup.....c105f5fc3660c185fe1f0f0d66f9579c