ANGIOTENSIN-II-ALDOSTERONE INTERACTIONS ON PROTEIN-SYNTHESIS IN VASCULAR SMOOTH-MUSCLE CELLS

We examined the effects of mineralocorticoid-mediated increases in ang iotensin II receptors on angiotensin II-stimulated protein synthesis i n cultured rat aortic vascular smooth muscle cells. Incubation of quie scent (serum-deprived) cells for 24 h with angiotensin II alone result ed in concentration-dependent increases in leucine incorporation (prot ein synthesis), e.g., 57% over control after 1 muM angiotensin II, whe reas incubation for 24 h with aldosterone alone resulted in concentrat ion-dependent decreases in leucine incorporation, e.g., 40% less than control after 1 muM aldosterone. Incubation of serum-replete cells wit h 10 nM aldosterone for 24 h followed by serum deprivation and incubat ion with 100 nM angiotensin II and 1 nM aldosterone for an additional 48 h (experimental conditions in which angiotensin II receptor number was increased but the direct negative effects of aldosterone on leucin e incorporation were minimized) resulted in increases in angiotensin I I-stimulated protein synthesis by 53%, and this augmentation was inhib ited by the aldosterone receptor antagonist spironolactone. The aldost erone effect was not universal, as aldosterone did not upregulate bind ing of or potentiate leucine incorporation stimulated by thromboxane A 2 mimetics; nor was the aldosterone effect mediated by inhibition of a ngiotensin II metabolism, because angiotensin II concentrations were n ot increased by incubation with aldosterone. In summary, aldosterone-m ediated increases in angiotensin II receptor number are associated wit h enhanced angiotensin II-stimulated protein synthesis.