Corticosteroids decrease glomerular angiotensin receptors.
Angiotensin II (ANG II) receptors of glomerular mesangial cells are regulated in vivo by changes in Na balance, effects that are presumed to be secondary to changes in circulating ANG II. However, since changes in ANG II were accompanied by parallel changes in plasma aldosterone in all models tested, it is possible that aldosterone may have also participated in the modulation of glomerular ANG II receptors. To test this hypothesis, short-term aldosterone infusions within the physiological range were employed to favor actions that would be mediated through a high-affinity mineralocorticoid receptor. The glucocorticoid, dexamethasone, was also tested to determine the mineralocorticoid specificity of the response. Two infusion rates were associated with a decrease in glomerular ANG II receptor density of 33 and 45%, respectively. There were no changes in the affinity of ANG II in either tissue or in adrenal receptor density. Serum potassium and urinary Na/K ratio were lower in the aldosterone group. Spironolactone abolished the effect of aldosterone consistent with an action mediated through a specific mineralocorticoid receptor. Dexamethasone administration produced similar downregulation of glomerular ANG II receptor and was unaccompanied by a change in electrolyte balance or blood volume. These studies support the hypothesis that corticosteroids modulate glomerular ANG II receptors and validate the complexity of glomerular receptor modulation. The downregulation observed would be expected to diminish the ability of ANG II to influence glomerular hemodynamics in models such as mineralocorticoid and glucocorticoid-induced hypertension.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000450:Aldosterone / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D006439:Hemodynamics; D007678:Kidney Glomerulus / Q000187:drug effects*; D008297:Male; D009318:Natriuresis; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013148:Spironolactone / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D013148:Spironolactone; D000450:Aldosterone; D012964:Sodium; D011188:Potassium