POTENTIAL ROLE OF 12-HYDROXYEICOSATETRAENOIC ACID IN ANGIOTENSIN-II-INDUCED CALCIUM SIGNAL IN RAT GLOMERULOSA CELLS

Recent evidence suggests that 12 hydroxyeicosatetraenoic acid (12HETE) , a product of the 12 lipoxygenase (LO) pathway of arachidonic acid me tabolism, may have a role in mediating angiotensin II (AII)-induced al dosterone secretion. The present study examined the possible role of t he 12 LO product 12HETE in AII-induced calcium ([Ca++]i) signals in ra t glomerulosa cells. The addition of 12HETE to glomerulosa cells induc ed a dose-dependent (10(-6) - 10(-8) M) rise in [Ca++]i levels that wa s sustained over 15 min. The effects of 12HETE on [Ca++]i were attenua ted but not blocked by nifedipine (5.10(-6) m) and were preserved in a calcium-free medium, suggesting mobilization of intracellular calcium stores. Furthermore, the 12HETE-mediated rise in [Ca++]i was almost e ntirely abolished by dantrolene. In parallel, 12HETE reversed the inhi bitory effect of nifedipine on AII-induced aldosterone secretion [All (10(-9) M) - 36 +/- 7, AII + nifedipine (5 - 10(-6) m) - 13 +/- 2, AII + nifedipine + 12HETE (5.10(-8) M) - 27 +/- 4 ng/10(6) cells]. Dantro lene also inhibited AII-dependent aldosterone secretion (AII 10(-9) M - 75.8 +/- 5.6, AII + dantrolene 10(-6) M 45.5 +/- 8.8 ng/10(-8) cells ), but this inhibition could not be reversed by 12HETE 10(-8) M (45.4 +/- 10.6 ng/10(6) cells). The LO blockers baicalein and BW755C inhibit ed the effect of AII on aldosterone production and on [Ca++]i in a par allel fashion. During LO blockade, the addition of 12HETE (10(-7) m) r estored the AII-induced rise in [Ca++]i. Collectively, these observati ons suggest that activation of the LO pathway in the rat adrenal glome rulosa contributes to changes in cytosolic calcium, which may be impor tant for the steroidogenic effect of AII.