Role for thromboxane receptors in angiotensin-II-induced hypertension.

Journal Article

To evaluate the role of thromboxane in hypertension and its complications, we studied mice with targeted disruption of the TXA2 receptor gene in an angiotensin-II-dependent model of hypertension. To determine whether genetic background might alter the physiological actions of the TP receptor, we studied two lines of TP knockout (Tp-/-) mice with distinct genetic backgrounds (C57BL/6 and BALB/c). During chronic angiotensin II infusion (1000 ng/kg per minute x 28 days by subcutaneous osmotic pump), TP deficiency prevented mortality in the C57BL/6 background but not in the BALB/c strain. Chronic angiotensin II infusion also caused a rapid and significant increase in blood pressure in wild-type (WT) C57BL/6 and BALB/c animals, which was significantly attenuated in Tp-/- mice on either background. After 28 days of infusion, cardiac hypertrophy only occurred in the C57BL/6 strain: heart/body weight ratio increased by 57%+/-8% in WT mice compared with 17%+/-6.5% for the Tp-/- mice (P<0.01). Chronic angiotensin II infusion caused albuminuria only in the C57BL/6 strain, and TP deficiency did not alter its development. Cyclooxygenase-1 knockout mice also had attenuated blood pressure increase during chronic angiotensin II infusion, suggesting that cyclooxygenase-1 metabolites are involved in angiotensin-II-dependent hypertension. Thus, on the C57BL/6 background, TP receptors contribute to cardiac hypertrophy but not proteinuria. However, irrespective of genetic background, the TP receptor makes a robust contribution to the pathogenesis of angiotensin II-dependent hypertension.

Full Text

Duke Authors

Cited Authors

  • Francois, H; Athirakul, K; Mao, L; Rockman, H; Coffman, TM

Published Date

  • February 2004

Published In

Volume / Issue

  • 43 / 2

Start / End Page

  • 364 - 369

PubMed ID

  • 14718360

Electronic International Standard Serial Number (EISSN)

  • 1524-4563

Digital Object Identifier (DOI)

  • 10.1161/01.HYP.0000112225.27560.24

Language

  • eng

Conference Location

  • United States