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Effects of angiotensin II and antagonists on AT(1) receptor expression in mesangial cells
D Chansel1, S Vandermeersch, C Llorens-Cortes
1INSERM U. 489, Hôpital Tenon, 4 rue de la Chine, 75020, Paris, France.
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.
Insights
Glucocorticoids inhibit angiotensin AT(1B) receptors in rat mesangial cells. Candesartan has complex effects, increasing mRNA but inhibiting protein, while other antagonists are inactive.
Area of Science:
- Nephrology
- Pharmacology
- Molecular Biology
Background:
- The renin-angiotensin system plays a crucial role in regulating kidney function.
- Angiotensin II receptor antagonists are widely used to treat hypertension and kidney diseases.
- Understanding the specific effects of these antagonists and other agents on receptor expression is vital.
Purpose of the Study:
- To investigate the effects of angiotensin II, specific AT(1) receptor antagonists (losartan, EXP 3174, candesartan), and dexamethasone on AT(1A) and AT(1B) receptor mRNA and protein expression in rat mesangial cells.
- To elucidate the differential regulation of angiotensin AT(1) receptor subtypes by various pharmacological agents.
Main Methods:
- Rat mesangial cells were treated with angiotensin II, losartan, EXP 3174, candesartan, or dexamethasone for 1-24 hours.
- Messenger RNA (mRNA) levels for angiotensin AT(1A) and AT(1B) receptors were quantified using reverse transcription-polymerase chain reaction (RT-PCR).
- Protein levels of the angiotensin AT(1) receptor were assessed by Western blot analysis.
Main Results:
- Angiotensin II, losartan, and EXP 3174 did not significantly alter AT(1A) or AT(1B) receptor mRNA or protein levels.
- Candesartan demonstrated a complex effect, increasing AT(1B) receptor mRNA and, to a lesser extent, AT(1A) receptor mRNA, while also inhibiting AT(1) receptor protein expression.
- Dexamethasone significantly decreased AT(1B) receptor mRNA and exerted an inhibitory effect on AT(1) receptor protein.
Conclusions:
- The angiotensin AT(1B) receptor subtype, predominantly expressed in rat mesangial cells, is inhibited by glucocorticoids.
- Candesartan exhibits a dual action: upregulating AT(1B) receptor mRNA while downregulating AT(1) receptor protein.
- Angiotensin II and losartan/EXP 3174 show no significant impact on angiotensin AT(1) receptor mRNA or protein expression in this cellular model.
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