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Changes of sodium and ATP affinities of the cardiac (Na,K)-ATase during and after nitric oxide deficient hypertension

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Abstract

In the cardiovascular system, NO is involved in the regulation of a variety of functions. Inhibition of NO synthesis induces sustained hypertension. In several models of hypertension, elevation of intracellular sodium level was documented in cardiac tissue. To assess the molecular basis of disturbances in transmembraneous transport of Na+, we studied the response of cardiac (Na,K)-ATPase to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day NG-nitro-L-arginine methyl ester (L-NAME) for 4 four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 36%. Two weeks after terminating the treatment, the SBP recovered to control value. When activating the (Na,K)-ATPase with its substrate ATP, no changes in Km and Vmax values were observed in NO-deficient rats. During activation with Na+, the Vmax remained unchanged, however the KNa increased by 50%, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After recovery from hypertension, the activity of (Na,K)-ATPase increased, due to higher affinity of the ATP-binding site, as revealed from the lowered Km value for ATP. The KNa value for Na+ returned to control value. Inhibition of NO-synthase induced a reversible hypertension accompanied by depressed Na+-extrusion from cardiac cells as a consequence of deteriorated Na+-binding properties of the (Na,K)-ATPase. After recovery of blood pressure to control values, the extrusion of Na+ from cardiac cells was normalized, as revealed by restoration of the (Na,K)-ATPase activity. (Mol Cell Biochem 000: 000-000, 1999)

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References

  1. Pecháňová O, Bernátová I: Effect of long-term NO synthase inhibition on cyclic nucleotide content in rat tissues. Physiol Res45: 305–309, 1996.

    PubMed  Google Scholar 

  2. Holécyová A, Török J, Bernátová I, Pecháňová O: Restriction of nitric oxide rather than the elevated blood pressure is responsible for alterations of vascular responses in nitric oxide deficient hypertension. Physiol Res 45: 317–321, 1996

    PubMed  Google Scholar 

  3. Kubes P, Suzuki M, Granger DN: Nitric oxide an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 88: 4651–4655, 1991

    PubMed  Google Scholar 

  4. Forstermann U, Closs EI, Pollock JS, Schwarz P, Gath I, Kleinert H: Nitric oxide synthase isozymes, characterization, purification, molecular cloning, and functions. Hypertension 23 1121–1131, 1994

    PubMed  Google Scholar 

  5. Forstermann U, Mügge A, Alheid U, Haverich A, Frölich JC: Selective attenuation of endothelium-mediated vasodilatation in atherosclerotic human coronary arteries. Circ Res 62: 185–190, 1988

    PubMed  Google Scholar 

  6. Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, Ganz P: Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 315: 1046–1051, 1986

    PubMed  Google Scholar 

  7. Török J, Gerová M: Vascular responses after long-term inhibition of nitric oxide synthesis in newborn dogs. Physiol Res 45: 323–328, 1996

    PubMed  Google Scholar 

  8. Amrani M, OnShea J, Allen NJ, Harding SE, Jayakumar J, Pepper JR, Moncada S, Yaeoab MH: Role of basal release of nitric oxide on coronary flow and mechanical performance of the isolated rat heart. J Physiol 456: 681–687, 1992

    PubMed  Google Scholar 

  9. Groenendaal F, Mishra OP, McGowan JE, Delivoria-Papadopoulos M: Brain cell membrane Na+,K+-ATPase activity after inhibition of cerebral nitric oxide synthase by intravenous NG-nitro-L-arginine in newborn piglets. Biol Neonate 68: 419–425,1995

    PubMed  Google Scholar 

  10. Gupta S, McArthur C, Grady C, Ruderman NB: Stimulation of vascular Na+-K+-ATPase activity by nitric oxide: A cGMP-independent effect. Am J Physiol 266: H2146–2151, 1994

    PubMed  Google Scholar 

  11. Gupta S, Moreland RB, Munarriz R, Daley J, Goldstein I, Saenz de Tejada I: Possible role of Na+-K+-ATPase in the regulation of human corpus cavernosum smooth muscle contractility by nitric oxide. Br J Pharmacol 116: 2201–2206, 1995

    PubMed  Google Scholar 

  12. Bredt DS, Snyder SH: Isolation of nitric oxide synthase, a calmodulinrequiring enzyme. Proc Natl Acad Sci USA 87: 682–685, 1990

    PubMed  Google Scholar 

  13. Bernátová I, Pecháňová O, Simko F: Captopril prevents NO-deficient hypertension and left ventricular hypertrophy without affecting nitric oxide synthase activity in rats. Physiol Res 45: 311–316, 1996

    PubMed  Google Scholar 

  14. Vrbjar N, Soós J, Ziegelhöffer A: Secondary structure of heart sarcolemmal proteins during interaction with metallic cofactors of (Na+ + K+)-ATPase. Gen Physiol Biophys 3: 317–325, 1984

    PubMed  Google Scholar 

  15. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275, 1951

    PubMed  Google Scholar 

  16. Taussky HH, Shorr EE: A microcolorimetric method for the determination of inorganic phosphorus. J Biol Chem 202: 675–685, 1953

    PubMed  Google Scholar 

  17. Bers DM, Philipson KD, Nishimoto AY: Sodium-calcium exchange and sidedness of isolated cardiac sarcolemmal vesicles. Biochim Biophys Acta 601: 358–371, 1980.

    PubMed  Google Scholar 

  18. Babál P, Pecháňová O, Bernátová I, Štvrtina S: Chronic inhibition of NO synthesis produces myocardial fibrosis and arterial media hyperplasia. Histol Histopathol 12: 623–629, 1997

    PubMed  Google Scholar 

  19. Ribeiro MO, Antunes E, de Nucci G, Lovisolo SM, Zatz R: Chronic inhibition of nitric oxide synthesis: a new model of arterial hypertension. Hypertension 20: 298–303, 1992

    PubMed  Google Scholar 

  20. Delacretaz E, Hayoz D, Osterheld MC, Genton CY, Brunner HR, Waeber B: Long-term nitric oxide synthase inhibition and distensibility of carotid artery in intact rats. Hypertension 23: 967–970, 1994

    PubMed  Google Scholar 

  21. Kristek F, Gerová M, Devát L, Varga I: Remodeling of septal branch of coronary artery and carotid artery in L-NAME treated rats. Physiol Res 45: 329–333, 1996

    PubMed  Google Scholar 

  22. Tepel M, Theilmeier G, Bachmann J, Barenbock M, Spieker C, Ganten D, Rahn KH, Zidek W: Increased cytosolic sodium and reduced Na,KATPase activity in transgenic rats. Hypertension 23: (suppl 1): 198–202, 1994

    Google Scholar 

  23. Jelicks LA, Gupta RK: Nuclear magnetic resonance measurement of intracellular sodium in the perfused normotensive and spontaneously hypertensive rat heart. Am J Hypertens 7: 429–435, 1994

    PubMed  Google Scholar 

  24. Slezák J, Schulze W, Štefánková Z, Okruhlicová L, Danihel L, Wallukat G: Localization of α 1,2,3-subunit isoforms of Na,K-ATPase in cultured neonatal and adult rat myocardium: The immunofluorescence and immunocytochemical study. Mol Cell Biochem 163/164: 39–45, 1996

    Google Scholar 

  25. Zahler R, Sun W, Ardito T, Kashgarian M: Na-K-ATPase α-isoform expression in heart and vascular endothelia: cellular and developmental regulation. Am J Physiol 270: C361–C371, 1996

    PubMed  Google Scholar 

  26. Zahler R, Gilmore-Hebert M, Baldwin JC, Franco K, Benz EJ: Expression of α isoforms of the Na,K-ATPase in human heart. Biochim Biophys Acta 1149: 189–194, 1993

    PubMed  Google Scholar 

  27. Herrera VLM, Chobanian AV, Ruiz-Opazo N: Isoform-specific modulation of Na+,K+-ATPase α-subunit gene expression in hypertension. Science 241: 221–223, 1988

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute for Heart Research, Department of Biochemistry, Slovak Academy of Sciences, Bratislavia

    Norbert Vrbjar

  2. Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislavia, Slovak Republic

    Iveta Bernátová & Ol'ga Pecháňová

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  1. Norbert Vrbjar
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  2. Iveta Bernátová
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  3. Ol'ga Pecháňová
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Vrbjar, N., Bernátová, I. & Pecháňová, O. Changes of sodium and ATP affinities of the cardiac (Na,K)-ATase during and after nitric oxide deficient hypertension. Mol Cell Biochem 202, 141–147 (1999). https://doi.org/10.1023/A:1007097617502

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