Regulation of the sodium pump during cardiomyocyte adaptation to pregnancy.

Regulation of the sodium pump during normal pregnancy and its effect on the function of cardiomyocytes is poorly understood. Our objective was to evaluate the possible implication of the Na(+)-K(+)-ATPase, the sodium pump which controls cellular ionic and metabolic homeostasis, in the adaptations of cardiomyocytes to normal pregnancy. We have used Western blots and patch-clamp measurements to identify changes in the sodium pump proteins. Confocal microscopy was applied to estimate intracellular sodium concentration. Time-resolved spectroscopy was employed to measure mitochondrial NAD(P)H fluorescence and estimate oxidative metabolic state. Optical microscopy was adopted to study the contractility responses of cardiomyocytes. Cells from non-pregnant and pregnant rats (1 day prior parturition) were studied. Our results showed lower protein expression of the α1 Na(+)-K(+)-ATPase isoform in cardiomyocytes in pregnant rats, decreased sodium pump membrane current and elevated steady-state sodium concentration. In addition, ouabain, the inhibitor of the sodium pump capable of increasing cardiomyocyte contractility in non-pregnant rats in a concentration-dependent manner, failed to affect cell contractions in pregnant rats. We also noted modified responsiveness of the mitochondrial metabolic state to ouabain in cardiac cells. The gathered data confirmed that in pregnant rats, the sodium pump protein content and transmembrane flux are decreased, while the sensitivity of cardiomyocyte contractility and the sensitivity of mitochondrial metabolic redox state to ouabain are modified, pointing to regulation of the Na(+)-K(+)-ATPase during cardiac cell adaptations to normal pregnancy.

Structural, functional and metabolic remodeling of rat left ventricular myocytes in normal and in sodium-supplemented pregnancy.

OBJECTIVES: Pregnancy is an important physiological condition associated with hemodynamic and endocrine changes that affect the heart. Nevertheless, very little is known about cardiomyocyte remodeling in this condition. Here, we studied the morphological, functional and metabolic remodeling of rat left ventricular myocytes that occurs in late stages of normal pregnancy (P) and in experimental preeclampsia induced by elevated (0.9%) sodium intake (P0.9). METHODS: We applied confocal microscopy to examine the morphology and the contractility of single cells, while the patch clamp technique was used to assay ionic currents. RESULTS: Our results revealed a significant increase in the volume of single left ventricular cardiac myocytes in P, mainly resulting from cell elongation. In P0.9, further increase in the cell length led to a significant rise in the length/width ratio. Cell contractility was significantly decreased in glucose-based solutions in response to stimulation at 0.5 Hz and 6 Hz in P as well as in P0.9. The density of L-type calcium current (I(Ca)L) was not significantly altered in P or in P0.9. Metabolic substrates lactate and pyruvate, increased in the blood of P and P0.9 rats, enhanced contractility in P, without affecting I(Ca)L. The same effect, present but blunted in P0.9, was associated with a significant increase in I(Ca)L. CONCLUSION: Our results demonstrate that processes of adaptive remodeling take place in normal pregnancy, while maladaptive components are identified in experimental preeclampsia; they also reveal an adaptation in the use of energy substrates in pregnancy and its impairment by sodium supplementation.