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• W2007305364 abstract "Background —Atrial natriuretic peptide (ANP) depresses contractility in left ventricular myocytes. Its expression is upregulated in pressure-overloaded hypertrophied hearts; however, the effects of ANP on contractility in hypertrophied myocytes are not known. Our aims were (1) to examine the cellular mechanisms of this depression in contractility in normal myocytes and (2) to test the hypothesis that the effects of ANP on contractility differ in hypertrophied myocytes from rats with ascending aortic stenosis. Methods and Results —We measured the myocyte shortening as an index of contractility, [Ca 2+ ] i with fluo 3, and pH i with seminaphthorhodafluor-1 (SNARF-1). In normal control myocytes (n=26), ANP caused a concentration-dependent depression of contractility and reduction in pH i . In the presence of 10 −6 mol/L ANP, fractional cell shortening was 78±5% of baseline ( P <0.05) and pH i was reduced by 0.16±0.04 U from baseline ( P <0.01) without changes in [Ca 2+ ] i . The magnitude of the depression of contraction caused by ANP was similar to that caused by intracellular acidification induced by an NH 4 Cl pulse. The effects of ANP on contractility and pH i were prevented in the presence of 5-( N -ethyl- N -isopropyl)-amiloride (EIPA), which inhibits the Na + /H + exchanger. In hypertrophied myocytes (n=23), ANP did not depress either myocyte contractility or pH i at concentrations of either 10 −8 , 10 −7 , or 10 −6 mol/L. ANP caused no change in pH i or the [Ca 2+ ] i transient in hypertrophied myocytes. The cGMP level was increased and Na + /H + exchanger mRNA levels were normal in left ventricles from aortic stenosis rats compared with controls. Conclusions —ANP directly depresses contractility in normal myocytes via intracellular acidification, which decreases myofilament [Ca 2+ ] i sensitivity. In contrast, ANP causes no effects on contractility and pH i in hypertrophied myocytes, suggesting a suppression in the coupling of the ANP-cGMP intracellular signaling pathway to the Na + /H + exchanger." @default.
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• W2007305364 title "Atrial Natriuretic Peptide Has Different Effects on Contractility and Intracellular pH in Normal and Hypertrophied Myocytes From Pressure-Overloaded Hearts" @default.
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• W2007305364 doi "https://doi.org/10.1161/01.cir.98.24.2760" @default.
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