Changes of sodium and ATP affinities of the renal Na,K-ATPase during and after nitric oxide-deficient hypertension.
The aim of this study was to assess the molecular basis of renal Na,K-ATPase disturbances in response to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day N(G)-nitro-L-arginine methyl ester (L-NAME) for four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 30 %. Three weeks after terminating the treatment, SBP recovered to control value. When activating the Na,K-ATPase with its substrate ATP, a 36 % increase in K(m) and 29 % decrease in V(max) values were observed in NO-deficient rats. During activation with Na+, the V(max) was decreased by 20 % and the K(Na) was increased by 111 %, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After spontaneous recovery from hypertension, the V(max) remained at the level as in hypertension for both types of enzyme activation. However, in the presence of lower concentrations of substrate which are of physiological relevance an improvement of the enzyme activity was observed as documented by return of K(m) for ATP to control value. The K(Na) value for Na+ was decreased by 27 % as compared to hypertension, but still exceeded the corresponding value in the control group by 55 % thus resulting in a partial restoration of Na+ affinity of Na,K-ATPase which was depressed as a consequence of NO-dependent hypertension.
Vrbjar
N
N
Department of Biochemistry, Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Javorková
V
V
Pechánová
O
O
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006977:Hypertension, Renal / Q000139:chemically induced / Q000201:enzymology*; D007668:Kidney / Q000201:enzymology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000172:deficiency*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D011921:Rats, Inbred WKY; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D012964:Sodium; D019001:Nitric Oxide Synthase; D000254:Sodium-Potassium-Exchanging ATPase; D019331:NG-Nitroarginine Methyl Ester