Deficiency of COX-1 causes natriuresis and enhanced sensitivity to ACE inhibition.

Journal Article (Journal Article)

BACKGROUND: Prostanoid products of the cyclo-oxygenase (COX) pathway of arachidonic acid metabolism modulate blood pressure (BP) and sodium homeostasis. Conventional non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit both COX isoforms (COX-1 and -2), cause sodium retention, exacerbate hypertension, and interfere with the efficacy of certain anti-hypertensive agents such as angiotensin-converting enzyme (ACE) inhibitors. While a new class of NSAIDs that specifically inhibit COX-2 is now widely used, the relative contribution of the individual COX isoforms to these untoward effects is not clear. METHODS: To address this question, we studied mice with targeted disruption of the COX-1 (Ptgs1) gene. Blood pressure, renin mRNA expression, and aldosterone were measured while dietary sodium was varied. To study interactions with the renin-angiotensin system, ACE inhibitors were administered and mice with combined deficiency of COX-1 and the angiotensin II subtype 1A (AT1A) receptor were generated. RESULTS: On a regular diet, BP in COX-1-/- mice was near normal. However, during low salt feeding, BP values were reduced in COX-1-/- compared to +/+ animals, and this reduction in BP was associated with abnormal natriuresis despite appropriate stimulation of renin and aldosterone. Compared to COX-1+/+ mice, the actions of ACE inhibition were markedly accentuated in COX-1-/- mice. Sodium sensitivity and BP lowering also were enhanced in mice with combined deficiency of COX-1 and AT1A receptor. CONCLUSIONS: The absence of COX-1 is associated with sodium loss and enhanced sensitivity to ACE inhibition, suggesting that COX-1 inhibition does not cause hypertension and abnormal sodium handling associated with NSAID use.

Full Text

Duke Authors

Cited Authors

  • Athirakul, K; Kim, HS; Audoly, LP; Smithies, O; Coffman, TM

Published Date

  • December 2001

Published In

Volume / Issue

  • 60 / 6

Start / End Page

  • 2324 - 2329

PubMed ID

  • 11737606

International Standard Serial Number (ISSN)

  • 0085-2538

Digital Object Identifier (DOI)

  • 10.1046/j.1523-1755.2001.00072.x


  • eng

Conference Location

  • United States