Angiotensin II stimulates secretion of endogenous ouabain from bovine adrenocortical cells via angiotensin type 2 receptors.

Angiotensin II stimulates secretion of corticosteroids and ouabain-like activity from adrenocortical cells. Distinct adrenocortical angiotensin II receptor subtypes (AT1, AT2) have been described, and the present studies investigated their roles in steroid secretion. Using primary bovine adrenocortical cell cultures under serum free conditions, angiotensin II stimulated the secretions of aldosterone, cortisol, and endogenous ouabain as verified by high-performance chromatography. The dose-response curves for stimulated steroid secretion were parallel with unitary slopes while the half-maximally effective concentrations of angiotensin II were 0.31 to 0.38 nmol/L for secretions of aldosterone and cortisol and 2.3 nmol/L for endogenous ouabain. The nonselective mammalian antagonist (Sar1-Ile8) angiotensin II blocked stimulated secretion of all three steroids without affecting basal output. In the presence of the AT1 antagonist DuP753, angiotensin II-stimulated secretions of aldosterone and cortisol were blocked while secretion of endogenous ouabain was unaffected. In the presence of the AT2 antagonist PD123319, both basal and angiotensin II-stimulated secretions of aldosterone and cortisol were normal while stimulated secretion of endogenous ouabain was inhibited. The secretion of endogenous ouabain was activated maximally by the AT2 agonist CGP42112 under conditions in which aldosterone secretion was unaffected. These results demonstrate that AT2 receptors stimulate secretion of endogenous ouabain from bovine adrenocortical cells. The specificity of AT1 and AT2 receptor stimulation indicates that separate signaling mechanisms having minimal cross talk control the adrenocortical secretions of corticosteroids and cardiac-active steroids. Adrenocortical AT2 receptors may be important in the adaptation to low salt diets and other conditions in which angiotensin II is increased.