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Journal of Physiology and Biochemistry

, Volume 64, Issue 2, pp 115–125 | Cite as

Chronic ouabain treatment increases the contribution of nitric oxide to endothelium-dependent relaxation

  • R. Aras-López
  • J. Blanco-Rivero
  • R. Hernanz
  • A. M. Briones
  • L. V. Rossoni
  • M. Ferrer
  • M. Salaices
  • G. Balfagon
Article

Abstract

The aim of this study was to analyze the contribution of nitric oxide, prostacyclin and endothelium-dependent hyperpolarizing factor to endothelium-dependent vasodilation induced by acetylcholine in rat aorta from control and ouabain-induced hypertensive rats. Preincubation with the nitric oxide synthase inhibitor N-omega-nitro-l-arginine methyl esther (L-NAME) inhibited the vasodilator response to acetylcholine in segments from both groups but to a greater extent in segments from ouabain-treated rats. Basal and acetylcholine-induced nitric oxide release were higher in segments from ouabain-treated rats. Preincubation with the prostacyclin synthesis inhibitor tranylcypromine or with the cyclooxygenase inhibitor indomethacin inhibited the vasodilator response to acetylcholine in aortic segments from both groups. The Ca2+-dependent potassium channel blocker charybdotoxin inhibited the vasodilator response to acetylcholine only in segments from control rats. These results indicate that hypertension induced by chronic ouabain treatment is accompanied by increased endothelial nitric oxide participation and impaired endothelium-dependent hyperpolarizing factor contribution in acetylcholine-induced relaxation. These effects might explain the lack of effect of ouabain treatment on acetylcholine responses in rat aorta.

Keywords

Nitric oxide Endothelial-dependent hyperpolarizing factor Prostacyclin Acetylcholine 

El tratamiento crónico con ouabaína incrementa la contribución del óxido nítrico a la relajación dependiente de endotelio

Resumen

Se analiza en este trabajo la contribución del óxido nítrico, la prostaciclina y el factor hiperpolarizante dependiente de endotelio (EDHF) en la vasodilatación inducida por acetilcolina en aorta de ratas controles y con hipertensión inducida por ouabaína. La preincubación con el inhibidor de la óxido nítrico sintasa N-omega-nitro-L-arginina metil éster (L-NAME) inhibió la respuesta vasodilatadora a acetilcolina en segmentos de ambos grupos experimentales, pero en mayor medida en los de ratas tratadas con ouabaína. La liberación de óxido nítrico basal e inducida por acetilcolina fue mayor en segmentos de animales tratados con ouabaína. La preincubación con tranilcipromina, inhibidor de la prostaciclina sintasa, y con indometacina, inhibidor de la ciclooxigenasa, inhibió la respuesta vasodilatadora a acetilcolina en segmentos de aorta de ambos grupos experimentales. El bloqueante de los canales de potasio dependientes de Ca2+, charibdotoxina, inhibió la respuesta vasodilatadora a acetilcolina sólo en segmentos de animales control. Estos resultados indican que la hipertensión inducida por el tratamiento crónico con ouabaína se acompaña de aumento en la participación del óxido nítrico endotelial y de disminución del efecto del EDHF mediado por canales de potasio dependientes de Ca2+ en la relajación inducida por acetilcolina. Estos efectos opuestos podrían explicar el hecho de que el tratamiento con ouabaína no modifique la respuesta a la acetilcolina.

Palabras clave

Óxido nítrico Factor hiperpolarizante dependiente de endotelio Prostaciclina Acetilcolina 

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Copyright information

© Universidad de Navarra 2008

Authors and Affiliations

  • R. Aras-López
    • 1
  • J. Blanco-Rivero
    • 1
  • R. Hernanz
    • 2
  • A. M. Briones
    • 2
  • L. V. Rossoni
    • 3
  • M. Ferrer
    • 1
  • M. Salaices
    • 2
  • G. Balfagon
    • 1
  1. 1.Departamentos de FisiologíaUniversidad Autónoma de MadridMadridSpain
  2. 2.Farmacología y Terapéutica, Facultad de MedicinaUniversidad Autónoma de MadridMadridSpain
  3. 3.Department of Physiology and Biophysics, Institute of Biomedical SciencesUniversity of São PauloSão PauloBrazil

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