Effects of angiotensin II and antagonists on AT 1 receptor expression in mesangial cells

Abstract

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.