Aliskiren, Both as Monotherapy and in Combination With Valsartan, Reduces Plasma Aldosterone in Patients With Hypertension: PP.24.457

Abstract

Background: Studies in transgenic rats expressing the human (pro)renin receptor have shown elevated plasma aldosterone levels in these animals despite unaffected plasma renin concentration or activity. It has been speculated that this is mediated through a direct effect of (pro)renin on aldosterone synthesis via the (pro)renin receptor ((P)RR). Other studies have shown an increased expression of adrenal CYP11B2 mRNA in these animals compared to wildtype despite unchanged levels of angiotensin II (Ang II). We evaluated the effect of (pro)renin on the expression of the main steroidogenic enzymes in an adrenocortical cell line (H295R).Methods: First, the expression of the (P)RR was tested by RT-PCR. Second, H295R cells (10^5 cells/mL) were serum-starved for 24 hours and subsequently incubated with Ang II (100 nM), phorbol-12-myristate-13-acetate (PMA, 10 nM), renin (1 and 10 nM), or prorenin (1 nM) for 6, 24 and 48 hours. After RNA isolation by standard methods, the expression of STAR, CYP11A1, HSD3B2, CYP21A2, CYP11B2, and CYP17A1 was measured by quantitative RT-PCR. To investigate whether an effect on aldosterone synthesis could be attributed to activation of the local renin-angiotensinsystem (RAS), ACE activity in H295R cells was assessed by measurement of Ang II formation after incubation with Ang I (10-8 M for 30, 60, 180 and 360 minutes).

Blood pressure and plasma renin activity responses to different strategies to inhibit the renin-angiotensin-aldosterone system during exercise

“…Currently there are two main strategies to inhibit RAAS: (a) direct renin inhibition (DRI), i.e. aliskiren, which inhibits the active site of renin and reduces PRA, 16,17 or (b) inhibition of RAAS downstream of renin, i.e., via inhibition of angiotensin-converting enzyme (ACE) or angiotensin receptor blockade (ARB). Both of these downstream RAAS inhibiting strategies result in increased PRA and the magnitude of PRA elevation is an index of their efficiency of RAAS inhibition.…”