Prostacyclin protects against elevated blood pressure and cardiac fibrosis.

Journal Article

Specific inhibitors of COX-2 have been associated with increased risk for cardiovascular complications. These agents reduce prostacyclin (PGI2) without affecting production of thromboxane (Tx) A2. While this abnormal pattern of eicosanoid generation has been implicated in the development of vascular disease associated with COX-2 inhibition, its role in the development of hypertension, the most common cardiovascular complication associated with COX-2 inhibition, is not known. We report here that mice lacking the receptor for PGI2 (IPKOs) develop salt-sensitive hypertension, cardiac hypertrophy, and severe cardiac fibrosis. Coincidental deletion of the TxA2 (TP) receptor does not prevent the development of hypertension, but cardiac hypertrophy is ameliorated and fibrosis is prevented in IPTP double knockouts (DKOs). Thus, deletion of the IP receptor removes a constraint revealing adverse cardiovascular consequences of TxA2. Our data suggest that adjuvant therapy that blocks unrestrained Tx actions might protect against end-organ damage without affecting blood pressure in patients taking COX-2 inhibitors.

Full Text

Duke Authors

Cited Authors

  • Francois, H; Athirakul, K; Howell, D; Dash, R; Mao, L; Kim, H-S; Rockman, HA; Fitzgerald, GA; Koller, BH; Coffman, TM

Published Date

  • September 2005

Published In

Volume / Issue

  • 2 / 3

Start / End Page

  • 201 - 207

PubMed ID

  • 16154102

International Standard Serial Number (ISSN)

  • 1550-4131

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2005.08.005

Language

  • eng

Conference Location

  • United States