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Effect of chronic hypoxia on voltage-independent calcium influx activated by 5-HT in rat intrapulmonary arteries.
- Source :
-
Pflugers Archiv : European journal of physiology [Pflugers Arch] 2007 Apr; Vol. 454 (1), pp. 41-51. Date of Electronic Publication: 2006 Dec 05. - Publication Year :
- 2007
-
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 TRPC(6) 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.
- Subjects :
- Animals
Calcium Channel Blockers pharmacology
Calcium Signaling drug effects
Cells, Cultured
Chronic Disease
Cyclohexanones pharmacology
Drug Resistance
Electrophysiology
Gadolinium pharmacology
Hypoxia physiopathology
In Vitro Techniques
Intracellular Membranes metabolism
Lipoprotein Lipase antagonists & inhibitors
Male
Myocytes, Smooth Muscle metabolism
Nitrendipine pharmacology
Pulmonary Artery drug effects
Pulmonary Artery metabolism
Pulmonary Artery pathology
Rats
Rats, Wistar
TRPC Cation Channels metabolism
Vasoconstriction drug effects
Calcium metabolism
Hypoxia metabolism
Pulmonary Artery physiopathology
Serotonin pharmacology
Vasoconstrictor Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0031-6768
- Volume :
- 454
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Pflugers Archiv : European journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 17146678
- Full Text :
- https://doi.org/10.1007/s00424-006-0178-y