心房利钠肽对压力超负荷心脏的正常和肥大心肌细胞的收缩性及细胞内pH有不同影响。

Atrial natriuretic peptide has different effects on contractility and intracellular pH in normal and hypertrophied myocytes from pressure-overloaded hearts.

作者信息

Tajima M, Bartunek J, Weinberg E O, Ito N, Lorell B H

机构信息

Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory of Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

出版信息

Circulation. 1998 Dec 15;98(24):2760-4. doi: 10.1161/01.cir.98.24.2760.

DOI:10.1161/01.cir.98.24.2760

PMID:9851964

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, [Ca2+]i with fluo 3, and pHi with seminaphthorhodafluor-1 (SNARF-1). In normal control myocytes (n=26), ANP caused a concentration-dependent depression of contractility and reduction in pHi. In the presence of 10(-6) mol/L ANP, fractional cell shortening was 78+/-5% of baseline (P<0.05) and pHi was reduced by 0.16+/-0.04 U from baseline (P<0.01) without changes in [Ca2+]i. The magnitude of the depression of contraction caused by ANP was similar to that caused by intracellular acidification induced by an NH4Cl pulse. The effects of ANP on contractility and pHi 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 pHi at concentrations of either 10(-8), 10(-7), or 10(-6) mol/L. ANP caused no change in pHi or the [Ca2+]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 [Ca2+]i sensitivity. In contrast, ANP causes no effects on contractility and pHi in hypertrophied myocytes, suggesting a suppression in the coupling of the ANP-cGMP intracellular signaling pathway to the Na+/H+ exchanger.

摘要

背景

心房利钠肽（ANP）可降低左心室心肌细胞的收缩力。在压力超负荷肥大心脏中其表达上调；然而，ANP对肥大心肌细胞收缩力的影响尚不清楚。我们的目的是：（1）研究正常心肌细胞收缩力降低的细胞机制；（2）验证以下假说，即ANP对收缩力的影响在升主动脉狭窄大鼠的肥大心肌细胞中有所不同。

方法与结果

我们测量了心肌细胞缩短情况作为收缩力指标，用Fluo 3测量细胞内钙浓度（[Ca2+]i），用半萘酚罗丹明氟-1（SNARF-1）测量细胞内pH值（pHi）。在正常对照心肌细胞（n = 26）中，ANP引起收缩力呈浓度依赖性降低以及pHi降低。在10^(-6)mol/L ANP存在时，细胞缩短分数为基线的78±5%（P<0.05），pHi较基线降低0.16±0.04单位（P<0.01），而[Ca2+]i无变化。ANP引起的收缩力降低幅度与氯化铵脉冲诱导的细胞内酸化引起的幅度相似。在存在抑制钠/氢交换体的5-（N-乙基-N-异丙基）-氨氯吡咪（EIPA）时，ANP对收缩力和pHi的影响被阻断。在肥大心肌细胞（n = 23）中，10^(-8)、10^(-7)或10^(-6)mol/L浓度的ANP均未降低心肌细胞收缩力或pHi。ANP对肥大心肌细胞的pHi或钙瞬变无影响。与对照组相比，主动脉狭窄大鼠左心室中环磷酸鸟苷（cGMP）水平升高，钠/氢交换体mRNA水平正常。