Myocardial PKC β2 and the Sensitivity of Na/K-ATPase to Marinobufagenin Are Reduced by Cicletanine in Dahl Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2003-03, Vol.41 (3), p.505-511
• Main Authors: Fedorova, Olga V, Talan, Mark I, Agalakova, Natalia I, Droy-Lefaix, Marie-Therese, Lakatta, Edward G, Bagrov, Alexei Y
• Format: Article
• Language: English
• Subjects: Antihypertensive agents; Biological and medical sciences; Cardiovascular system; Medical sciences; Pharmacology. Drug treatments
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000053446.43894.9F

ABSTRACT—Marinobufagenin (MBG), an endogenous ligand of α-1 Na/K-ATPase, becomes elevated and contributes to hypertension in NaCl-loaded Dahl-S rats (DS). Protein kinase C (PKC) phosphorylates α-1 Na/K-ATPase and increases its MBG sensitivity. Cicletanine, an antihypertensive compound with PKC-inhibitory activity, reverses MBG-induced Na/K-ATPase inhibition and vasoconstriction. We hypothesized that increased PKC levels in sodium-loaded hypertensive DS would sensitize α-1 Na/K-ATPase to MBG and that PKC inhibition by cicletanine would produce an opposite effect. We studied the effects of cicletanine on systolic blood pressure, left ventricular PKC isoforms, cardiac α-1 Na/K-ATPase levels, and sensitivity to MBG in hypertensive DS. Seven DS received 50 mg · kg · d cicletanine, and 7 DS received vehicle during 4 weeks of an 8% NaCl diet. Vehicle-treated rats exhibited an increase in blood pressure, left ventricular mass, MBG excretion (74±11 vs 9±1 pmol/24 h, P