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Pharmacology. 2013;91(1-2):29-34. doi: 10.1159/000343762. Epub 2012 Nov 9.

Novel anti-inflammatory effects of doxazosin in rodent models of inflammation.

Author information

1
BioMed Valley Discoveries, Kansas City, MO 64111, USA. dtung@biomed-valley.com

Abstract

BACKGROUND:

Doxazosin is an α(1)-adrenergic receptor antagonist for the treatment of high blood pressure and benign prostatic hyperplasia. Peripheral α-adrenergic receptors have been implicated in inflammation.

AIM:

To examine the anti-inflammatory effects of doxazosin in rodent models of inflammation.

METHOD:

The anti-inflammatory properties of doxazosin were investigated in 4 models. In all studies, drug treatment was administered 15 min prior to challenge. In the lipopolysaccharide (LPS)-induced systemic inflammation model, LPS was injected systemically at 0.25 mg/kg. At 90 min after challenge, blood samples were collected for analysis. In the LPS-induced pulmonary inflammation model, LPS was instilled intranasally. Four hours after challenge, the lungs were harvested for monocyte chemoattractant protein-1 (MCP-1) analysis. In a delayed-type hypersensitivity model, the mice were injected intravenously with sheep red blood cells, and rechallenged in the left footpad 7 days later. Drug treatment was given on day 6 and 7 just prior to the rechallenge. The thickness of hind footpads was measured at 15 min after rechallenge. In the thioglycollate-induced peritoneal monocyte infiltration model, mice were challenged with 3% thioglycollate, and 2 h later peritoneal lavage fluid was collected for MCP-1 analysis.

RESULTS:

In animals challenged systemically and intranasally with LPS, doxazosin inhibited TNF-α and MCP-1 production, respectively. In the delayed-type hypersensitivity model, footpad swelling was inhibited by doxazosin. Doxazosin decreased the level of MCP-1 release in the peritoneal cavity of thioglycollate-stimulated animals, though this effect was not statistically significant.

CONCLUSION:

This is the first set of studies that reports the novel anti-inflammatory effects of doxazosin.

PMID:
23146878
DOI:
10.1159/000343762
[Indexed for MEDLINE]

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