Effect of chronic hypoxia on voltage-independent calcium influx activated by 5-HT in rat intrapulmonary arteries |
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Authors: | Lise Rodat Jean-Pierre Savineau Roger Marthan Christelle Guibert |
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Institution: | (1) Université Bordeaux2, Laboratoire de Physiologie Cellulaire Respiratoire, 146, rue Léo Saignat, F33076 Bordeaux;, INSERM, E356, F33076 Bordeaux, France |
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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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Keywords: | Chronic hypoxia TRP Voltage-independent calcium influx Serotonin Calcium signaling Vascular smooth muscle |
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