Both aldosterone and spironolactone can modulate the intracellular ACE/ANG II/AT1 and ACE2/ANG (1 ‐7)/MAS receptor axes in human mesangial cells

Aldosterone stimulation can modulate the intracellular RAAS of immortalized human mesangial cells by evaluating both the axes ACE/ANG II/AT ‐1 and ACE2/ANG‐ (1‐7)/Mas axes AbstractThe kidney is an important target of the renin ‐ANG‐aldosterone system (RAAS). To date, several studies have demonstrated the existence of a local RAAS in various tissues, including the renal tissue. The mineralocorticoid aldosterone is known to play a critical role in the classical RAAS; however, its effect on mesangial cells (MCs) remains to be elucidated. Based on this, our aim was to investigate whether aldosterone stimulation can modulate the intracellular RAAS of immortalized human MCs by evaluating ANG‐converting enzyme (ACE)/ANG II/ANG II receptor type 1 (AT1) and ANG‐converting enzyme 2 (ACE2)/ANG (1‐7)/MAS receptor axes . To realise this, protein expression, enzyme activity, and immunofluorescence were performed under aldosterone stimulation and in the presence of the mineralocorticoid receptor (MR) antagonist spironolactone (SPI). We observed that high doses of aldosterone increase ACE activity. The effect of aldo sterone on the catalytic activity of ACE was completely abolished with the pretreatment of SPI suggesting that the aldosterone‐induced cell injuries through ANG II release were attenuated. Aldosterone treatment also decreased the expression of MAS receptor, but did not alter the expression or the catalytic activity of ACE 2 and ANG (1‐7) levels. Spironolacton...
Source: Physiological Reports - Category: Physiology Authors: Tags: Original Research Source Type: research