Angiotensin II-aldosterone interactions on protein synthesis in vascular smooth muscle cells.
We examined the effects of mineralocorticoid-mediated increases in angiotensin II receptors on angiotensin II-stimulated protein synthesis in cultured rat aortic vascular smooth muscle cells. Incubation of quiescent (serum-deprived) cells for 24 h with angiotensin II alone resulted in concentration-dependent increases in leucine incorporation (protein synthesis), e.g., 57% over control after 1 microM angiotensin II, whereas incubation for 24 h with aldosterone alone resulted in concentration-dependent decreases in leucine incorporation, e.g., 40% less than control after 1 microM aldosterone. Incubation of serum-replete cells with 10 nM aldosterone for 24 h followed by serum deprivation and incubation 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 leucine incorporation were minimized) resulted in increases in angiotensin II-stimulated protein synthesis by 53%, and this augmentation was inhibited by the aldosterone receptor antagonist spironolactone. The aldosterone effect was not universal, as aldosterone did not upregulate binding of or potentiate leucine incorporation stimulated by thromboxane A2 mimetics; nor was the aldosterone effect mediated by inhibition of angiotensin II metabolism, because angiotensin II concentrations were not increased by incubation with aldosterone. In summary, aldosterone-mediated increases in angiotensin II receptor number are associated with enhanced angiotensin II-stimulated protein synthesis.
Ullian
M E
ME
Department of Medicine, Medical University of South Carolina, Charleston 29425.
Hutchison
F N
FN
Hazen-Martin
D J
DJ
Morinelli
T A
TA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000450:Aldosterone / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D004357:Drug Synergism; D007930:Leucine / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism; D015854:Up-Regulation
D009124:Muscle Proteins; D011450:Prostaglandin Endoperoxides, Synthetic; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000450:Aldosterone; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003907:Dexamethasone; D007930:Leucine