AT1 receptor antagonism is proangiogenic in the brain

Bdnf a novel mediators

Ahmed Alhusban, Anna Kozak, Adviye Ergul, Susan C. Fagan

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Candesartan is an angiotensin II type 1 receptor blocker (ARB) that has been to shown to limit ischemic stroke and improve stroke outcome. In experimental stroke, candesartan induces a proangiogenic effect that is partly attributable to vascular endothelial growth factor. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that has been reported to have angiogenic effects and play an important role in recovery after stroke. The purpose of this investigation was to determine the role of BDNF in the proangiogenic effect of candesartan in the brain under hypertensive conditions. Accordingly, spontaneously hypertensive rats were treated with candesartan, and brain tissue samples were collected for quantification of BDNF expression. In addition, human cerebromicrovascular endothelial cells were treated with either low-dose (1M) or high-dose (1 μM) angiotensin II alone or in combination with candesartan (0.16 μM) to assess the effect of candesartan treatment and BDNF involvement in the behavior of endothelial cells. Candesartan significantly increased the expression of BDNF in the SHR (P <0.05). In addition, candesartan reversed the antiangiogenic effect of the 1-μM dose of AngII (P < 0.0001). The observed effects of candesartan were ablated by neutralizing the effects of BDNF. Treatment with the AT2 antagonist PD-123319 significantly reduced tube-like formation in endothelial cells. AT2 stimulation induced the BDNF expression and migration (P < 0.05). In conclusion, candesartan exerts a proangiogenic effect on brain microvascular endothelial cells treated with angiotensin II. This response is attributable to increased BDNF expression and is mediated through stimulation of the AT 2 receptor.

Original languageEnglish (US)
Pages (from-to)348-359
Number of pages12
JournalJournal of Pharmacology and Experimental Therapeutics
Volume344
Issue number2
DOIs
StatePublished - Feb 1 2013

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Brain-Derived Neurotrophic Factor
Brain
Endothelial Cells
Stroke
Angiotensin II
candesartan
Angiotensin II Type 1 Receptor Blockers
Nerve Growth Factors
Inbred SHR Rats
Vascular Endothelial Growth Factor A

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

AT1 receptor antagonism is proangiogenic in the brain : Bdnf a novel mediators. / Alhusban, Ahmed; Kozak, Anna; Ergul, Adviye; Fagan, Susan C.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 344, No. 2, 01.02.2013, p. 348-359.

Research output: Contribution to journalArticle

Alhusban, Ahmed ; Kozak, Anna ; Ergul, Adviye ; Fagan, Susan C. / AT1 receptor antagonism is proangiogenic in the brain : Bdnf a novel mediators. In: Journal of Pharmacology and Experimental Therapeutics. 2013 ; Vol. 344, No. 2. pp. 348-359.
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