Primary aldosteronism (PA), in which plasma aldosterone levels are normal or elevated relative to suppressed plasma renin levels, is the most frequent cause of secondary hypertension. PA accounts for 5-10% of hypertension cases and up to 20% in those with resistant hypertension. Aldosterone is a mineralocorticoid hormone responsible for maintaining fluid volume, electrolyte balance, and blood pressure homeostasis; it is tightly regulated by the renin-angiotensin-aldosterone system. Our laboratory has previously shown that phospholipase D2 (PLD2) mediates angiotensin II-induced aldosterone synthesis and secretion in vitro. Therefore, we hypothesized that PLD2 loss would result in decreased aldosterone production in vivo. To test this hypothesis, 11-week-old male and female wild-type and PLD2-/- mice were fed a high salt (1% NaCl) or a low salt (0.02% NaCl; to raise endogenous serum angiotensin II levels) diet for 24 hours. Adrenal steroidogenic gene expression and serum aldosterone, corticosterone, and electrolytes were measured by qRT-PCR, radioimmunoassay, ELISA, and atomic absorption spectrometry, respectively. The PLD2-/- male mice exhibited increased StAR, Dab2, and CYP11B1 expression; further, PLD2 loss impaired low salt-induced increases in StAR, Dab2, and CYP11B1 expression; however, PLD2 loss had no effect on CYP11B2 expression or serum aldosterone, Na+ , K+ , and corticosterone levels in these male mice. These data suggest that increased steroidogenic enzyme expression may compensate for PLD2 loss in order to maintain aldosterone secretion in the males. On the other hand, the PLD2-/- female mice exhibited decreased StAR and CYP11B1 expression and serum Na+ levels as well as impaired low salt-induced increases in StAR, CYP11B2, Dab2, and CYP11B1 expression. PLD2 loss had no effect on serum aldosterone, K+ , or corticosterone levels in these female mice. It is possible that other compensatory mechanisms (not involving steroidogenic enzymes) might be involved in maintaining aldosterone secretion in the females. Together, our findings suggest a likely importance of PLD2 in mediating aldosterone production and steroidogenic enzyme gene expression, with differential effects in male and female mice.
|Original language||English (US)|
|Journal||FASEB journal : official publication of the Federation of American Societies for Experimental Biology|
|State||Published - May 1 2022|
ASJC Scopus subject areas
- Molecular Biology