Effects of cardiotonic steroids on isolated perfused kidney and NHE3 activity in renal proximal tubules

Biochimica Et Biophysica Acta. General Subjects
Alana N GodinhoNilberto R F do Nascimento

Abstract

Cardiotonic steroids (CS) are known as modulators of sodium and water homeostasis. These compounds contribute to the excretion of sodium under overload conditions due to its natriuretic property related to the inhibition of the renal Na+/K+-ATPase (NKA) pump α1 isoform. NHE3, the main route for Na+ reabsorption in the proximal tubule, depends on the Na+ gradient generated by the NKA pump. In the present study we aimed to investigate the effects of marinobufagin (MBG) and telocinobufagin (TBG) on the renal function of isolated perfused rat kidney and on the inhibition of NKA activity. Furthermore, we investigated the mechanisms for the cardiotonic steroid-mediated natriuretic effect, by evaluating and comparing the effects of bufalin (BUF), ouabain (OUA), MBG and TBG on NHE3 activity in the renal proximal tubule in vivo. TBG significantly increased GFR, UF, natriuresis and kaliuresis in isolated perfused rat kidney, and inhibits the activity of NKA at a much higher rate than MBG. By stationary microperfusion technique, the perfusion with BUF, OUA, TBG or MBG promoted an inhibitory effect on NHE3 activity, whereas BUF was the most effective agent, and demonstrated a dose-dependent response, with maximal inhibition at 50nM. Furthe...Continue Reading

Citations

Jan 28, 2020·Pain Reports·Geissy I M C FeitosaKrishnamurti M Carvalho
Jun 27, 2019·Journal of Immunology Research·Deyse C M CarvalhoSandra Rodrigues-Mascarenhas
Sep 19, 2018·International Journal of Molecular Sciences·Luciana S AmaralLuis Eduardo M Quintas

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