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Abstract

Angiotensin II down-regulates the vascular smooth muscle AT1 receptor by transcriptional and post-transcriptional mechanisms: evidence for homologous and heterologous regulation.

B Lassègue, R W Alexander, G Nickenig, M Clark, T J Murphy and K K Griendling
Molecular Pharmacology October 1995, 48 (4) 601-609;
B Lassègue
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R W Alexander
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G Nickenig
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M Clark
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T J Murphy
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K K Griendling
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Abstract

The vascular angiotensin II (ANG II) receptor (AT1) is a central component of the renin-angiotensin system; thus, regulation of its expression is likely to be important in cardiovascular responsiveness. We demonstrate that ANG II down-regulates its receptor in rat aortic vascular smooth muscle cells. Incubation for 4 hr with 100 nM ANG II decreased AT1 mRNA and protein by 70% and 35%, respectively. This homologous down-regulation was concentration and time dependent and was blocked by the AT1 antagonist losartan. It did not appear to be mediated by protein kinase C or other protein kinases but was dependent on the sustained signaling pathway sensitive to phenylarsine oxide. Heterologous down-regulation was observed with the agonists alpha-thrombin and ATP and the cAMP-increasing agent forskolin. ANG II inhibited transcription by 50% and destabilized the AT1 mRNA. Down-regulation of AT1 mRNA was blocked by transcription and translation inhibitors, suggesting that it required expression of a protein factor or factors. These results indicate that ANG II down-regulates its vascular receptor by both transcriptional and post-transcriptional mechanisms. Homologous and heterologous down-regulation of the AT1 receptor may participate in the coordinated physiological adaptation of vascular tone to vasoactive hormones.

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Molecular Pharmacology
Vol. 48, Issue 4
1 Oct 1995
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Abstract

Angiotensin II down-regulates the vascular smooth muscle AT1 receptor by transcriptional and post-transcriptional mechanisms: evidence for homologous and heterologous regulation.

B Lassègue, R W Alexander, G Nickenig, M Clark, T J Murphy and K K Griendling
Molecular Pharmacology October 1, 1995, 48 (4) 601-609;

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Abstract

Angiotensin II down-regulates the vascular smooth muscle AT1 receptor by transcriptional and post-transcriptional mechanisms: evidence for homologous and heterologous regulation.

B Lassègue, R W Alexander, G Nickenig, M Clark, T J Murphy and K K Griendling
Molecular Pharmacology October 1, 1995, 48 (4) 601-609;
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