Dual effect of polyphenolic compounds on cardiac Na+/K+-ATPase during development and persistence of hypertension in rats.
The enzyme kinetics of cardiac Na(+)/K(+)-ATPase were used for characterizing the ATP- and Na(+)-binding sites after administration of red wine polyphenolic compounds (Provinol) during developing and sustained hypertension. Hypertension was induced in rats (LN group) by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 40 mg*kg(-1)*day(-1)). Provinol (40 mg*kg(-1)*day(-1)) was applied during developing hypertension (LNPF4 group) and sustained hypertension (LNPF7/3 group). Provinol reduced the number of active Na(+)/K(+)-ATPase molecules in cardiac tissue, as indicated by decreased V(max) values (by 33% in LNPF4 and 26% in LNPF7/3 compared with LN). Concerning qualitative properties of the enzyme, Provinol induced different effects on the ATP- and Na(+)-binding sites of Na(+)/K(+)-ATPase. The ATP-binding site was impaired by Provinol, as indicated by increased K(m) value (by 52% in LNPF4 vs. LN), suggesting worsened utilization of substrate by the enzyme. In sustained hypertension, however, Provinol had no effect on the ATP-binding site, as indicated by unchanged K(m) value (LNPF7/3 vs. LN). On the other hand, the Na(+)-binding site was protected by Provinol, as suggested by decreased K(Na) value (by 72% in LNPF4 and 69% in LNPF7/3 vs. LN), indicating an increased affinity of the enzyme for sodium. Thus, Provinol appeared to stimulate the extrusion of Na(+) from cardiac cells, especially in the physiologically important range of sodium concentrations (2-10 mmol*L(-1)), during both developing and sustained hypertension.
Vlkovicová
Jana
J
Institute for Heart Research, Department of Biochemistry, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Javorková
Veronika
V
Mézesová
Lucia
L
Pechánová
Olga
O
Andriantsitohaina
Ramaroson
R
Vrbjar
Norbert
N
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D011921:Rats, Inbred WKY; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism
D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D019001:Nitric Oxide Synthase; D000254:Sodium-Potassium-Exchanging ATPase; D019331:NG-Nitroarginine Methyl Ester