Pflügers Archiv - European Journal of Physiology

, Volume 466, Issue 2, pp 237–251 | Cite as

Genetic deletion of aquaporin-1 results in microcardia and low blood pressure in mouse with intact nitric oxide-dependent relaxation, but enhanced prostanoids-dependent relaxation

  • V. Montiel
  • E. Leon Gomez
  • C. Bouzin
  • H. Esfahani
  • M. Romero Perez
  • I. Lobysheva
  • O. Devuyst
  • C. DessyEmail author
  • J. L. BalligandEmail author
Integrative physiology


The water channels, aquaporins (AQPs) are key mediators of transcellular fluid transport. However, their expression and role in cardiac tissue is poorly characterized. Particularly, AQP1 was suggested to transport other molecules (nitric oxide (NO), hydrogen peroxide (H2O2)) with potential major bearing on cardiovascular physiology. We therefore examined the expression of all AQPs and the phenotype of AQP1 knockout mice (vs. wild-type littermates) under implanted telemetry in vivo, as well as endothelium-dependent relaxation in isolated aortas and resistance vessels ex vivo. Four aquaporins were expressed in wild-type heart tissue (AQP1, AQP7, AQP4, AQP8) and two aquaporins in aortic and mesenteric vessels (AQP1–AQP7). AQP1 was expressed in endothelial as well as cardiac and vascular muscle cells and co-segregated with caveolin-1. AQP1 knockout (KO) mice exhibited a prominent microcardia and decreased myocyte transverse dimensions despite no change in capillary density. Both male and female AQP1 KO mice had lower mean BP, which was not attributable to altered water balance or autonomic dysfunction (from baroreflex and frequency analysis of BP and HR variability). NO-dependent BP variability was unperturbed. Accordingly, endothelium-derived hyperpolarizing factor (EDH(F)) or NO-dependent relaxation were unchanged in aorta or resistance vessels ex vivo. However, AQP1 KO mesenteric vessels exhibited an increase in endothelial prostanoids-dependent relaxation, together with increased expression of COX-2. This enhanced relaxation was abrogated by COX inhibition. We conclude that AQP1 does not regulate the endothelial EDH or NO-dependent relaxation ex vivo or in vivo, but its deletion decreases baseline BP together with increased prostanoids-dependent relaxation in resistance vessels. Strikingly, this was associated with microcardia, unrelated to perturbed angiogenesis. This may raise interest for new inhibitors of AQP1 and their use to treat hypertrophic cardiac remodeling.


Aquaporins Blood pressure NO-dependent and independent endothelial function pathway Prostaglandins 



The authors are grateful to Yvette Cnops and Huguette Debaix from the Nephrology laboratory (NEFR/IREC), for their help in the RTqPCR and given some specifics primers for different aquaporins. VM is “Specialist doctorant” of the Fonds National de Recherche Scientifique (FNRS) and was supported by grants from the Fondation Saint Luc and FNRS (to JLB). CD is senior research scientist of the Fonds National de Recherche Scientifique (FNRS). CB is IREC imaging platform coordinator. These studies were supported in part by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant no. 305608 (EURenOmics), the Actions de Recherche Concertées (ARC 10/15-029 and 11/16-039, Communauté Française de Belgique), the FNRS and FRSM, and the Inter-University Attraction Pole (Belgium Federal Government). The Aqp1 mice were initially obtained from A.S. Verkman (University of California, San Francisco, CA).

Ethical standards

The experiments comply with the current laws of Belgium.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • V. Montiel
    • 1
    • 2
  • E. Leon Gomez
    • 1
  • C. Bouzin
    • 1
  • H. Esfahani
    • 1
  • M. Romero Perez
    • 1
  • I. Lobysheva
    • 1
  • O. Devuyst
    • 2
    • 3
  • C. Dessy
    • 1
    Email author
  • J. L. Balligand
    • 1
    • 2
    Email author
  1. 1.Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC)Université catholique de LouvainBrusselsBelgium
  2. 2.Department of MedicineCliniques Universitaires Saint-LucBrusselsBelgium
  3. 3.Pole of Nephrology (NEFR), Institut de Recherche Expérimentale et Clinique (IREC)Université catholique de LouvainBrusselsBelgium

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