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¹ Institute for Heart Research, Department of Biochemistry, Slovak Academy of Sciences, PO Box 104, 840 05 Bratislava 104, Slovak Republic² Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, 813 71 Bratislava, Slovak Republic³ Pharmacologie et Physico–Chimie des Interactions Cellulaires et Moléculaires, Université Louis Pasteur de Strasbourg, Unité Mixte de Recherche Centre National de la Recherche Scientifique 7034, Faculté Pharmacie, Illkirch, France

It has been suggested that polyphenolic substances provide protection against the risk factors of cardiovascular diseases. The present study was designed to investigate whether application of red wine polyphenols influences the kinetic properties of the renal Na⁺,K⁺-ATPase in rats with hypertension (164 ± 8 mmHg) that was experimentally induced by the NO synthase inhibitor N^G.-nitro-Larginine methyl ester (L-NAME). Polyphenols in a dose of 40 mg kg^–1 day^–1 in drinking fluid induced different effects on the properties of the renal Na⁺,K⁺-ATPase depending on the mode of their administration. Preventive application of polyphenols during the development of hypertension (144 ± 5 mmHg) partially protected the Na⁺,K⁺-ATPase molecule against hypertension-induced deterioration via increased capability of the enzyme to bind ATP and/or Na⁺ as suggested by decrease of K_m and K_Na, respectively, even to values lower than in controls. However, polyphenols did not prevent the hypertension-induced reduction of the number of active Na⁺,K⁺-ATPase molecules as shown by similar V_max values as compared to the hypertensive L-NAME group. The above protection is probably secured by a NO-dependent mechanism as suggested by 150% increase of the NO synthesis. Additional treatment of already hypertensive animals with polyphenols (153 ± 8 mmHg) resulted in partial restoration of the Na⁺,K⁺-ATPase affinities especially for sodium as indicated by significant diminution of K_Na. However, polyphenols in this mode of application did not slow down the L-NAME-induced decrease in the number of Na⁺,K⁺-ATPase molecules in the kidney as suggested by additional significant decrease in V_max values when comparing this group with the control group and also the hypertensive L-NAME group. In this case the polyphenols affected the Na,K-ATPase molecule in a NO-independent way as indicated by the fact that polyphenols failed to restore normal NO synthesis.

(Received 17 June 2003; accepted after revision 10 October 2003)
Corresponding author Norbert Vrbjar: Institute for Heart Research, Department of Biochemistry, Slovak Academy of Sciences, Dúbravská cesta 9, PO Box 104, 840 05 Bratislava 45, Slovak Republic. Email: usrdnorb{at}savba.sk