Effects of angiotensin II and antagonists on AT(1) receptor expression in mesangial cells.
Rat mesangial cells were exposed to angiotensin II, angiotensin AT(1) receptor antagonists such as losartan, EXP 3174 and candesartan, or dexamethasone for increasing periods (1-24 h). Angiotensin AT(1A) and AT(1B) receptor mRNA were measured by reverse transcription-polymerase chain reaction (RT-PCR). Angiotensin II, losartan and EXP 3174 did not modify significantly angiotensin AT(1A) and AT(1B) receptor mRNA. Candesartan increased angiotensin AT(1B) receptor mRNA and, to a lesser extent, angiotensin AT(1A) receptor mRNA. In contrast, dexamethasone decreased mainly angiotensin AT(1B) receptor mRNA. As shown by Western blot analysis, exposure of mesangial cells to angiotensin II, losartan or EXP 3174 did not produce any change in angiotensin AT(1) receptor protein, whereas dexamethasone and candesartan exerted inhibitory effects. In conclusion, the angiotensin AT(1B) receptor subtype, the most abundantly distributed in rat mesangial cells, is inhibited by glucocorticoids. The effect of candesartan is more complex with a slight stimulation of angiotensin AT(1B) mRNA and a marked inhibition of angiotensin AT(1) receptor protein. In contrast, angiotensin II and the other angiotensin AT(1) receptor antagonists studied are inactive on angiotensin AT(1) mRNA and protein.
Chansel
D
D
INSERM U. 489, Hôpital Tenon, 4 rue de la Chine, 75020, Paris, France.
Vandermeersch
S
S
Llorens-Cortes
C
C
Ardaillou
R
R
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007093:Imidazoles; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D003907:Dexamethasone; C066026:losartan carboxylic acid; D019808:Losartan; C081643:candesartan