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Effect of chronic hypoxia on voltage-independent calcium influx activated by 5-HT in rat intrapulmonary arteries

  • Cardiovascular System
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Abstract

5-Hydroxytryptamine (5-HT) is a potent pulmonary vasoconstrictor and mitogenic agent whose concentration increases in pulmonary hypertensive patients. Chronic hypoxia induces selective pulmonary arterial hypertension; therefore, we investigated chronic hypoxia effect on the calcium and contractile responses to 5-HT focusing on voltage-independent calcium influx in rat intrapulmonary arteries. Chronic hypoxia, induced by introducing rats in a hypobaric chamber for 3 weeks, potentiated the contraction to 5-HT and this effect was insensitive to nitrendipine. Calcium signal to 5-HT was characterized by a transient followed by a sustained phase in both normoxia and chronic hypoxia. The sustained phase was dependent on extracellular calcium and inhibited by lanthanum. RHC 80267, a specific inhibitor of diacylglycerol lipase, reduced the 5-HT-induced calcium influx in chronic hypoxia but not in normoxia. Furthermore, unlike gadolinium, RHC 80267 inhibited more the contraction to 5-HT in chronic hypoxia. Despite the apparent role of voltage-independent calcium channels in chronic hypoxia, Western blot and flow cytometry analyses demonstrated no variations in TRPC6 expression. This study shows for the first time that the 5-HT-induced calcium and contractile signals in chronic hypoxia are more dependent on a voltage-independent, RHC 80267-sensitive calcium influx and the hyperreactivity to 5-HT may thus be explained by this influx.

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Acknowledgements

We thank Huguette Crevel for her technical assistance and Thomas Trian for his help in performing FACS analysis. This work was supported by the Conseil Régional d’Aquitaine (200220301301A) and the Fondation de France (2006005603) and Lise Rodat was funded by the Fondation pour la Recherche Médicale (FRM- M. Josso).

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Authors and Affiliations

  1. Université Bordeaux2, Laboratoire de Physiologie Cellulaire Respiratoire, 146, rue Léo Saignat, F33076 Bordeaux;, INSERM, E356, F33076 Bordeaux, France

    Lise Rodat, Jean-Pierre Savineau, Roger Marthan & Christelle Guibert

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  1. Lise Rodat
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  2. Jean-Pierre Savineau
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  3. Roger Marthan
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  4. Christelle Guibert
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Correspondence to Christelle Guibert.

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Rodat, L., Savineau, JP., Marthan, R. et al. Effect of chronic hypoxia on voltage-independent calcium influx activated by 5-HT in rat intrapulmonary arteries. Pflugers Arch - Eur J Physiol 454, 41–51 (2007). https://doi.org/10.1007/s00424-006-0178-y

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  • DOI: https://doi.org/10.1007/s00424-006-0178-y

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