title: Enhanced relaxation to the rho-kinase inhibitor Y-27632 in mesenteric arteries from mineralocorticoid hypertensive rats.
abstract: Increased vasoconstriction is characteristic of hypertension. In this study, we tested the hypothesis that changes in vascular responses during mineralocorticoid hypertension may be due to increased activation of the Rho/Rho-kinase pathway. To test this, relaxation responses to the Rho-kinase inhibitor Y-27632 were determined by measuring isometric force in deendothelialized mesenteric arteries from mineralocorticoid-hypertensive rats and sham-operated controls. Following agonist-induced contraction by serotonin (5-HT, 5-hydroxytryptamine), arteries from hypertensive rats demonstrated a greater relaxation to the Rho-kinase inhibitor Y-27632 (65 +/- 5% vs. 28 +/- 10%). Treatment with an EC50 concentration of Y-27632 following a KCl-induced contraction caused minimal relaxation of arteries in both groups of animals. These findings suggest that augmented Rho-kinase activity in the vasculature of mineralocorticoid hypertensive rats may contribute to the enhanced vascular reactivity of agonist-mediated stimuli characteristic of this model of hypertension.
authors.affiliation: Department of Physiology, Medical College of Georgia, 120 Fifteenth Street, Augusta, GA 30912-3000, USA. dweber@psych.mcg.edu
authors.forename: D S
authors.initials: DS
authors.lastname: Weber
authors.forename: R C
authors.initials: RC
authors.lastname: Webb
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D003900:Desoxycorticosterone; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D054460:rho-Associated Kinases
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C108830:Y 27632; D012701:Serotonin; D003900:Desoxycorticosterone; D011189:Potassium Chloride; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases