Premium
Rat Strain Differences in Pulmonary Artery Smooth Muscle Ca 2+ Entry Following Chronic Hypoxia
Author(s) -
Snow Jessica B.,
Kanagy Nancy L.,
Walker Benjimen R.,
Resta Thomas C.
Publication year - 2009
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680903114268
Subject(s) - hypoxia (environmental) , endocrinology , medicine , endothelin 1 , protein kinase c , vascular smooth muscle , pulmonary artery , pulmonary hypertension , chemistry , vasodilation , endothelium , receptor , smooth muscle , pharmacology , kinase , biochemistry , oxygen , organic chemistry
Effects of chronic hypoxia (CH) on store‐ and receptor‐operated Ca 2+ entry (SOCE, ROCE) in pulmonary vascular smooth muscle (VSM) are controversial, although whether genetic variation explains such discrepancies in commonly studied rat strains is unclear. Since protein kinase C (PKC) can inhibit Ca 2+ permeable nonselective cation channels, we hypothesized that CH differentially alters PKC‐dependent inhibition of SOCE and ROCE in pulmonary VSM from Sprague‐Dawley and Wistar rats. To test this hypothesis, we examined SOCE and endothelin‐1 (ET‐1)‐induced ROCE in endothelium‐disrupted, pressurized pulmonary arteries from control and CH Sprague‐Dawley and Wistar rats. Basal VSM Ca 2+ was elevated in CH Wistar, but not Sprague‐Dawley, rats. Further, CH attenuated SOCE in VSM from Sprague‐Dawley rats, while augmenting this response in Wistar rats. CH reduced ROCE in arteries from both strains. PKC inhibition restored SOCE in CH Sprague‐Dawley arteries to control levels, while having no effect on SOCE in Wistar arteries or on ROCE in either strain. We conclude that effects of CH on pulmonary VSM SOCE are strain dependent, whereas inhibitory effects of CH on ROCE are strain independent. Further, PKC inhibits SOCE following CH in Sprague‐Dawley, but not Wistar, rats but does not contribute to ET‐1‐induced ROCE in either strain.