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.

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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