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Calcium sensitization underlies endothelium‐dependent hypoxic augmentation in the porcine coronary artery
Author(s) -
Vanhoutte Paul M,
Chan Calvin K
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.671.7
Subject(s) - calcium , thapsigargin , chemistry , endothelium , extracellular , hypoxia (environmental) , nifedipine , calcium in biology , medicine , nitric oxide , egta , endocrinology , voltage dependent calcium channel , biochemistry , oxygen , organic chemistry
In isolated porcine coronary arteries hypoxia (PO 2 :30 mm Hg) causes endothelium‐dependent potentiation (hypoxic augmentation) of contractions to vasoconstrictor agonists. Previous studies show that the presence of nitric oxide (NO), but not cyclic GMP, is a prerequisite for this augmentation to occur. Experiments were designed to determine the calcium‐dependency of the phenomenon. Rings (with or without endothelium) of porcine coronary arteries were suspended in organ chambers for the measurement of isometric tension, contracted with the TP receptor agonist U46619 and exposed to hypoxia. Incubation with a voltage operated calcium channel inhibitor (nifedipine) or calcium free buffer did not significantly affect hypoxic augmentation, while the calcium chelator EGTA abolished it. Hypoxia caused no significant increase in intracellular calcium concentration (detected by confocal fluorescence microscopy) in vascular smooth muscle. However, incubation with the Rho kinase inhibitors HA1077 or Y27632 reduced the response while thapsigargin significantly augmented it. These results suggest that hypoxic augmentation requires calcium, but does not depend on influx of extracellular calcium or an increase in the intracellular concentration of the activator ion. Thus, the endothelium‐dependent, NO‐requiring hypoxic augmentation involves calcium sensitization mediated by Rho kinase.