Cicletanine exhibits a concentration-dependent dual effect on Na+-H+ exchanger activity in chick embryonic cardiomyocytes, modulating intracellular pH recovery after acid load.
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Biphasic NHE effects in embryonic cardiomyocytes warrant dosing caution; leaves open therapeutic relevance pending mammalian and human studies.
Na+-H+ exchanger is thought to play an important role in the regulation of the intracellular pH (pHi) and in the cardiac cell injury induced by ischemia and reperfusion. The aim of this study was to assess the effect of cicletanine, an antihypertensive compound in humans, which has been reported to have cardioprotective effect under an ischemia-reperfusion process, on Na+-H+ exchanger activity in ventricular cardiomyocytes isolated from chick embryo. Na+-H+ exchanger activity was assessed by the rate of pHi recovery after an acid load. A dual effect was observed: at low concentration of cicletanine (10(-7) M), Na+-H+ exchanger activity was significantly decreased, whereas at higher concentrations (10(-6)-10(-5) M), a significant stimulation of the exchanger was observed. These results suggest that cicletanine modulates pHi recovery in cardiac cells after cellular acid load.
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Samain et al. (1999) studied this question.
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