Title

Aldosterone improves contractile function of adult rat ventricular cardiomyocytes in a non-acute way: potential relationship to the calcium paradox of aldosteronism

Document Type

Article

Department

Paediatrics and Child Health (East Africa)

Abstract

Heart failure is accompanied by electrolyte disturbance including reduced calcium and sodium in the extracellular milieu but increased calcium within cells, a phenomenon called “calcium paradox”. Aldosteronism is considered as part of this disorder. Aldosterone antagonism is known to reduce cardiac mortality on top of standard therapies such as antagonism of the renin–angiotensin-system. However, the effect of aldosterone on cardiac function under basal conditions and conditions more closely related to those seen in heart failure remains elusive. In order to address this question the function of isolated cardiomyocytes was determined as unloaded cell shortening. Cardiomyocytes were isolated from adult rat hearts and cultured for 24 h in the presence of aldosterone. Thereafter, cell shortening was determined in cells that were electrically paced (0.5–2.0 Hz). The effect of aldosterone on cell shortening was investigated under basal and maximal inotropic stimulation, preincubation with angiotensin II and myocytes from spontaneously hypertensive rats. The composition of the culture medium was modified according to the extracellular milieu found in patients with end-stage heart failure. Aldosterone increased cell shortening in a frequency-dependent way under basal conditions and conditions of low calcium. It potentiated the effect of β-adrenoceptor stimulation, increased the formation of oxygen radicals, and increased diastolic and systolic calcium. In conclusion, chronic exposure to aldosterone improves the function of cardiomyocytes under basal conditions and electrolyte disturbances that mimic the situation found in heart failure patients.

Comments

This work was published before the author joined Aga Khan University.

Publication

Basic Research in Cardiology

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