Downregulation of L-type voltage-gated Ca2+, voltage-gated K+, and large-conductance Ca2+-Activated K+ channels in vascular myocytes from salt-loading offspring rats exposed to prenatal hypoxia

Abstract

Background--Prenatal hypoxia is suggested to be associated with increased risks of hypertension in offspring. This study tested whether prenatal hypoxia resulted in salt-sensitive offspring and its related mechanisms of vascular ion channel remodeling. Methods and Results--Pregnant rats were housed in a normoxic (21% O2) or hypoxic (10.5% O2) chamber from gestation days 5 to 21. A subset of male offspring received a high-salt diet (8% NaCl) from 4 to 12 weeks after birth. Blood pressure was significantly increased only in the salt-loading offspring exposed to prenatal hypoxia, not in the offspring that received regular diets and in control offspring provided with high-salt diets. In mesenteric artery myocytes from the salt-loading offspring with prenatal hypoxia, depolarized resting membrane potential was associated with decreased density of L-type voltage-gated Ca2+ (Cav1.2) and voltagegated K+ channel currents and decreased calcium sensitive to the large-conductance Ca2+-activated K+ channels. Protein expression of the L-type voltage-gated Ca2+ α1C subunit, large-conductance calcium-activated K+ channel (β1, not α subunits), and voltage-gated K+ channel (KV2.1, not KV1.5 subunits) was also decreased in the arteries of salt-loading offspring with prenatal hypoxia. Conclusions--The results demonstrated that chronic prenatal hypoxia may program salt-sensitive hypertension in male offspring, providing new information of ion channel remodeling in hypertensive myocytes. This information paves the way for early prevention and treatments of salt-induced hypertension related to developmental problems in fetal origins.