Abstract 1984 Poster Session II, Sunday, 5/2 (poster 177)

Aldosterone plays a central role in the control of extracellular fluid (ECF) volume homeostasis. During chronic extracellular volume contraction induced by sodium depletion, Angiotensin II (AngII) mediates the secretion of aldosterone acting through specific receptors located in the zona glomerulosa of the adrenal gland (ZGAD). However, a recent study using mutant mice with a targeted deletion of the angiotensinogen gene have been shown that potassium can function as a regulatory signal for aldosterone synthesis and release even in the absence of an intact renin-angiotensin system (J. Clin. Invest. 99: 855-860, 1977). These investigators have proposed the existence of a mechanism independent of angiotensin for the activation of aldosterone secretion during ECF volume depletion. Here, we tested the hypothesis that the serum potassium levels per se, would modulate the expression of AngII receptors in the ZGAG, and that the effects of K+ in the adrenal gland might not be completely independent from the renin angiotensin system (RAS). The serum potassium and urinary aldosterone levels, plasma renin activity (PRA), and the number of Ang II receptors in the ZGAG in control and chronic volume contracted young rats were measured by quantitative autoradiography. Chronic ECF volume contraction (21 days) was induced by the following treatments: 1) Selective sodium 0.005% Na + depletion; 2) Selective chloride 0.005 %Cl- depletion; 3) Potassium 0.05% K + depletion; 4) Angiotensinogen depletion (sodium depleted [0.05% Na+] young rats treated with 10 mg enalapril/daily)(n = 5 rats each group). Statistical differences between groups were determined by ANOVA and multiple comparisons between treatments by the Student-Neuman-Keul's test. Both sodium depleted and angiotensinogen depleted rats showed significantly elevated serum potassium levels (> 5 mmol/l), in correlation with increased urinary aldosterone levels (> 20 ng/24 h), and up-regulation of AngII receptors in the ZGAG (>35% increased). However, PRA was increased in sodium depleted rats (>6 folds) and decreased (50%) in angiotensinogen depleted rats, when compared to control rats respectively. In contrast, chloride or potassium depleted rats showed reduced serum potassium levels (< 3 mmol/l), no changes in urinary aldosterone (2.4 ng/24h), and down-regulation of AngII receptors in the ZGAG (< 35%), when compared to control rats respectively, despite the high PRA levels (> 6 fold increase) found in both groups. In conclusion, this study clearly demonstrates that at least in young rats, the potassium-dependent mechanism for aldosterone release during ECF volume contraction is not completely independent from the RAS. Moreover, these results suggest that the serum potassium levels can directly modulate the number of AngII receptors in the ZGAG independently from the circulating levels of AngII.