title: Chronic ouabain treatment induces Rho kinase activation.
abstract: Ouabain is an endogenous Na(+)/K(+)-ATPase inhibitor whose chronic administration induces hypertension. Endogenous ouabain levels increase in human essential hypertension. On the other hand, Rho/Rho kinase (ROCK) pathway has been implicated in various animal models of hypertension. In the current work, we evaluated the possible involvement of Rho kinase in ouabain-induced hypertension. Ouabain was administered daily (20 µg/kg, i.p.) to Wistar rats for 6 weeks. After the ouabain treatment, we evaluated the possible changes in vascular responses to KCl and phenylephrine alone and in the presence of Rho kinase inhibitor Y27632. We also determined the expressions of ROCKs, Rho A and phosphorylation of myosin binding subunit of myosin light chain phosphatase (pMYPT) and activation of Rho A. Agonist-induced contractions in the presence of Y27632 are significantly decreased and Y27632-induced relaxations in aortas precontracted with phenylephrine are significantly enhanced with the chronic treatment of ouabain. Although the expressions of ROCK I and ROCK II remained unchanged, pMYPT expression was significantly increased in ouabain-treated group. Moreover, Rho A expression and activation were decreased after treatment with ouabain. Although Rho kinase expression did not change in aortas, increased basal Rho kinase activation may contribute to the development of ouabain-induced hypertension. Our current data present the first evidence that Rho kinase is involved in the development of ouabain-induced hypertension in rats.
authors: Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
authors: Aysun
authors: A
authors: Ozdemir
authors: Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
authors: Gürkan
authors: G
authors: Şahan
authors: Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
authors: Ayşegül
authors: A
authors: Demirtaş
authors: Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
authors: Eda
authors: E
authors: Aypar
authors: Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
authors: Gürkan
authors: G
authors: Gözübüyük
authors: Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
authors: Nilüfer Nermin
authors: NN
authors: Turan
authors: Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey. mark@gazi.edu.tr.
authors: Mustafa
authors: M
authors: Ark
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000633:toxicity; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D043263:Myosin-Light-Chain Phosphatase / Q000235:genetics / Q000378:metabolism*; D010042:Ouabain / Q000008:administration & dosage / Q000633:toxicity*; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D011725:Pyridines; C108830:Y 27632; D010656:Phenylephrine; D010042:Ouabain; D011189:Potassium Chloride; C578418:ROCK1 protein, rat; C580818:ROCK2 protein, rat; D054460:rho-Associated Kinases; D043263:Myosin-Light-Chain Phosphatase
keywords: Hypertension; Na+/K+-ATPase; Ouabain; ROCK; pMYPT