Sodium and ATP affinities of the cardiac Na(+),K(+)-ATPase in spontaneously hypertensive rats.
The Na(+),K(+)-ATPase is postulated to be involved in systemic vascular hypertension through its effects on smooth muscle reactivity and cardiac contractility. Investigating the kinetic properties of the above enzyme we tried to assess the molecular basis of alterations in transmembrane Na(+)-efflux from cardiac cells in spontaneously hypertensive rats (SHR). In the investigated group of SHR the systolic blood pressure and the heart weight were increased by 48% and by 60%, respectively. Upon activating the cardiac Na(+),K(+)-ATPase with substrate, its activity was lower in SHR in the whole concentration range of ATP. Evaluation of kinetic parameters revealed a decrease of the maximum velocity (Vmax) by 28% which was accompanied with lowered affinity of the ATP-binding site as indicated by the increased value of Michaelis-Menten constant (Km) by 354% in SHR. During activation with Na(+), we observed an inhibition of the enzyme in hearts from SHR at all tested Na(+) concentrations. The value of Vmax decreased by 37%, and the concentration of Na(+) that gives half maximal reaction velocity (KNa) increased by 98%. This impairment in the affinity of the Na(+)-binding site together with decreased affinity to ATP in the molecule of the Na(+),K(+)-ATPase are probably responsible for the deteriorated efflux of the excessive Na(+) from the intracellular space in hearts of SHR.
Vrbjar
N
N
Institute for Heart Research, Department of Biochemistry, Slovak Academy of Sciences, Bratislava, Slovakia. usrdnorb@savba.sk
Wachalová
K
K
Sipola
M
M
Vapaatalo
H
H
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D004789:Enzyme Activation; D006973:Hypertension / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009929:Organ Size; D011485:Protein Binding; D051381:Rats; D011921:Rats, Inbred WKY; D012016:Reference Values; D012508:Sarcolemma / Q000201:enzymology; D012964:Sodium / Q000737:chemistry / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism*
D000255:Adenosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase