Effect of dibutyryl cyclic AMP on plasma renin activity in normal men and patients with primary aldosteronism

Abstract

Dibutyryl cyclic AMP (DBcAMP) directly stimulates the release of renin from the juxtaglomerular (JG) cells in vitro. We investigated the effect of DBcAMP on plasma renin activity (PRA) in 6 normal men and in 8 patients with primary aldosteronism (PA). A 20-min infusion of 0.33 mg/kg/min of DBcAMP significantly increased PRA in normal men, but had little effect on PRA in patients with PA. Infusion of DBcAMP significantly reduced the blood pressure and the levels of serum sodium and potassium in normal men and the patients with PA. Infusion of DBcAMP significantly increased urine volume in normal men, but not in patients with PA. Urinary excretion of sodium increased in both groups after the infusion of DBcAMP. Thus, DBcAMP did not stimulate renin release in patients with PA, suggesting that the chronic excess production of aldosterone suppresses the release of renin from JG cells.

Role of Cyclic ADP-Ribose-Ca²⁺ Signaling in Mediating Renin Production and Release in As4.1 Cells

“…The active renin content (renin release) and total (active and inactive) renin content were measured as described previously [28][29]. In brief, after culture of the As4.1 cells, the medium was removed and kept for renin release measurement, and the cell were washed twice with phosphate buffered saline (PBS) and then harvested and frozen in liquid nitrogen and store at -80°C.…”

“…To measure total renin content in As4.1 cells, the samples (900 µl) were incubated at 0°C for 60 min with 100 µl of 4 mg/ml trypsin (Sigma) in 500 mM Tris buffer, pH=7.5, containing 5 mM CaCl 2 , 0.1% NaCl azide, and 1% bovine serium albumin as described previously [28][29]. Soybean trypsin inhibitor (Sigma; 8 mg/ml final concentration) was added to stop the reaction.…”