Aldosterone mediates angiotensin II-stimulated rat vascular smooth muscle cell proliferation.
Aldosterone, possibly locally generated, has been suggested to have a role in potentiating angiotensin II (AII)-stimulated hypertrophy of cultured vascular smooth muscle cells. To examine the possibility that aldosterone may mediate the proliferative actions of AII, rat aortic smooth muscle cells (RASMCs) in culture were treated with AII in the presence and absence of the specific AII type 1 receptor (AT1) antagonist, losartan, and aldosterone was assayed in culture medium extracts by radioimmunoassay. AII significantly enhanced aldosterone formation (at 10(-8) M: 123.8+/-14.85 vs control 71. 28+/- 8.71 fmol/10(5) cells, P<0.05; at 10(-7) M: 172.38+/-33.44, P<0.05), but not in the presence of losartan (at 10(-8) M: 53. 71+/-18.73, P>0.05; at 10(-7) M: 89.68+/-25.05, P>0.05). In other studies, the reverse transcriptase-polymerase chain reaction, performed on RNA extracted from RASMCs using aldosterone synthase (CYP11B2) specific primers, gave a single band of about 268 bp, consistent with that expected for the enzyme. Finally, using [(3)H]methylthymidine uptake as an index of cellular proliferation, tritium incorporation was increased in the AII-treated group at concentrations greater than 10(-10) M. The aldosterone antagonist, spironolactone (10(-5) M), inhibited the incorporation of [(3)H]thymidine into RASMCs stimulated by AII. These results suggest that locally generated aldosterone may mediate the effects of AII, acting via the AT1 receptor, in stimulating RASMC proliferation.
Xiao
F
F
Molecular and Cellular Biology, Division of Biomedical Sciences, Queen Mary and Westfield College, University of London, UK.
Puddefoot
J R
JR
Vinson
G P
GP
D000450:Aldosterone / Q000032:analysis / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001011:Aorta; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D019405:Cytochrome P-450 CYP11B2 / Q000032:analysis; D004357:Drug Synergism; D019808:Losartan / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013148:Spironolactone / Q000494:pharmacology; D013268:Stimulation, Chemical
D057911:Angiotensin Receptor Antagonists; D000451:Mineralocorticoid Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D013148:Spironolactone; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D019808:Losartan