title: Rat strain differences in pulmonary artery smooth muscle Ca(2+) entry following chronic hypoxia.
abstract: 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.
authors.affiliation: Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131-0001, USA. jsnow@salud.unm.edu
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Snow
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Kanagy
authors.forename: Benjimen R
authors.initials: BR
authors.lastname: Walker
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Resta
mesh_terms: D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002908:Chronic Disease; D019332:Endothelin-1 / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011651:Pulmonary Artery / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013045:Species Specificity
chemical_list: D019332:Endothelin-1; D011493:Protein Kinase C; D002118:Calcium