Diabetes modifies the role of prostanoids and potassium channels which regulate the hypereactivity of the rabbit renal artery to BNP

  • José M. Centeno
  • Luis Miranda-Gómez
  • Mikahela A. López-Morales
  • Teresa Jover-Mengual
  • María C. Burguete
  • Vannina G. Marrachelli
  • María Castelló-Ruiz
  • Alicia Aliena-Valero
  • Enrique Alborch
  • Francisco J. Miranda
Original Article


Diabetic nephropathy is associated with increased risk of cardiovascular disease. B-type natriuretic peptide (BNP) plays an important role in cardiovascular pathophysiology and therapeutics. The aim of the present study was to investigate the influence of experimental diabetes on the mechanisms that regulate the relaxant response of the rabbit renal artery to BNP. Arterial relaxations to BNP were enhanced in diabetic rabbits. Indomethacin enhanced BNP-induced relaxation in control rabbits but showed no effect in diabetic rabbits. BNP-induced release of thromboxane A2 or prostacyclin was not different in both groups of animals. Iberiotoxin had no effect on relaxations to BNP in both groups of animals. Charybdotoxin displaced to the right the concentration-response curve to BNP in both group of animals, and inhibited BNP-induced relaxation only in diabetic rabbits. Glibenclamide did not modify the BNP-induced relaxations in control rabbits, but inhibited it in diabetic rabbits. These results suggest that diabetes induces hypereactivity of the rabbit renal artery to BNP by mechanisms that at least include (1) a reduced vasoconstrictor influence of arachidonic acid metabolites via cyclooxygenase 2, which is not related with changes in thromboxane A2 and prostacyclin release from the arterial wall and (2) a selectively increased modulatory activity of KATP and endothelial IKCa channels.


B-type natriuretic peptide Diabetes Potassium channels Prostanoids Renal artery 



The authors are grateful to Salvador Banacloche for his technical assistance.

Funding information

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Ethical approval

Housing conditions and experimental procedures were performed in strict compliance with the European Union (Directive 2010/63/EU) and Spanish (RD 53/2013) regulations on the use of animals for scientific purposes and approved by the Ethics Committee for Animal Experimentation and Welfare from the University of Valencia (ref. A11295344586921).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • José M. Centeno
    • 1
  • Luis Miranda-Gómez
    • 1
  • Mikahela A. López-Morales
    • 1
  • Teresa Jover-Mengual
    • 1
  • María C. Burguete
    • 1
  • Vannina G. Marrachelli
    • 1
  • María Castelló-Ruiz
    • 2
  • Alicia Aliena-Valero
    • 1
  • Enrique Alborch
    • 1
  • Francisco J. Miranda
    • 1
    • 3
  1. 1.Unidad Mixta de Investigación Cerebrovascular (UMIC), Departamento de FisiologíaUniversidad de Valencia–Instituto de Investigación Sanitaria La FeValenciaSpain
  2. 2.Departamento de Biología Celular, Biología Funcional y Antropología FísicaUniversidad de ValenciaValenciaSpain
  3. 3.Departamento de Fisiología, Facultad de FarmaciaUniversidad de ValenciaBurjassotSpain

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