ORIGINAL ARTICLES Effects ofLong-Term, High-Altitude Hypoxia on Tension andIntracellular Calcium Responses in Coronary Arteries ofFetal andAdult Sheep

OBJECTIVES:We have previously shown that after exposure to long-termhypoxia,fetalcoronary flow ismaintained atcontrol levels despite a25%reduction incardiac output. Wealso demonstrated that coronary vascular rings isolated fromthelong-term hypoxic fetuses andstudied inwell-oxygenated bathsystem displayed significantly reduced depolarization-induced contraction strength inresponse toKCI.Tostudy the mechanism ofreduced fetal coronaryvascular responses toKCl-induced contractions following exposure to long-term hypoxia, we measured tension andintracellular calcium simultaneously, aswell asL-type Ca2+ channel density andsensitivity. METHODS: Pregnant eweswerehoused ataltitude (3820 m)for approximately 110days. At138to 141days ofgestation, long-term hypoxic andcontrol animals werekilled andjetal andadult left anterior descending coronaryartery (LAD) was isolated andstudied inawell-oxygenated bath system. Tension and intracellular calcium ([Ca2± _i) weremeasured simultaneously inresponse toincreasing concentrations ofKCl and, inaddition, thesensitivity tothecalcium channel blocker nfedipine was measured ata haff maximal concentration ofKCl.Wealso measured L-type Ca2+channel density with(+)-j3H]PN200- 110. RESULTS:L-type Ca2+channel density wasdecreased by-'31%inthelong-term hypoxicfetal, butnot adult, LAD.Tension inthelong-term hypoxicfetal andadult LAD was significantly lower atall concentrations ofKCl. [Ca2+1i was lower at rest in both fetaland adult LADfrom long-termhypoxic animals andincreased tolower levels atall concentrations ofKCI.Theratio oftension tofCa2+]i was also lower atall concentrations ofKCI.Sensitivity ton~fedipine was unchanged. CONCLUSIONS:Thereduced L-type Ca2+channel density andthereduced [Caa2+]i response toKCI, as well as thereduced tension responseto[Ca2+]i, could potentially beinvolved inthereduction in depolarization-induced contractions inLADfromlong-term hypoxicfetuses. Inhypoxic adults, reduced [Ca2+]i andreduced tension responseto[Ca2+1i may beinvolved inthelower tension responseto KCl-induced contractions. (USocGynecol Investig 2006; 13:11-8) Copyright C 2006bytheSociety forGynecologic Investigation.