Effects of High Potassium Diet on Angiotensin II Receptors and Angiotensin-Induced Aldosterone Production in Rat Adrenal Glomerulosa Cells*

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Abstract
Alterations in potassium (K+) balance modulate the sensitivity of the aldosterone secretory response to angiotensin II, but the mechanism of this change has not been elucidated. The present study was undertaken to evaluate the role of angiotensin II receptor alterations in this phenomenon. The effects of high K+ diet, on receptor binding of [l25I]angiotensin II and angiotensin-stimulated aldosterone production have been compared using isolated rat adrenal glomerulosa cells. A decrease in the equilibrium association constant occurred from the control value of 0.8 ± 0.2 to 0.4 ± 0.09 nM−1 (n = 8; P< 0.025). All values are the mean ± SEM. The change in equilibrium association constant was associated with a decrease in sensitivity of aldosterone responses to angiotensin II, as evidenced by increases in the angiotensin II concentration at half-maximum aldosterone production. The half-maximum aldosterone production was 1.0 ± 0.25 nM (n = 6) in control cells, 1.5 ± 0.03 nM (n = 3) at 3 days on a high potassium diet, and 1.94 ± 0.07 nM (n = 3; P< 0.025) at 7 days. A high K+ diet was also associated with an increase in angiotensin II receptor concentration to 3 times the control level. A progressive increase in maximum angiotensin II-stimulated aldosterone production occurred. The 8.1-fold maximum response to angiotensin II at 3 days and 14-fold maximum response at 7 days were both significantly higher than control cells (4- fold). These studies demonstrated that K+-induced changes in angiotensin II receptor content and affinity parallel alterations in angiotensin II-stimulated aldosterone production. Cells prepared from potassium-loaded rats also exhibited a more sensitive and higher maximum response to ACTH, suggesting that postreceptor changes are an important accompaniment as well. Changes in potassium balance are important regulators of adrenal angiotensin II receptors and are also important modulators of steroid responses to multiple stimuli. (Endocrinology106: 983, 1980)