Downregulation of L‐Type Voltage‐Gated Ca(2+), Voltage‐Gated K(+), and Large‐Conductance Ca(2+)‐Activated K(+) Channels in Vascular Myocytes From Salt‐Loading Offspring Rats Exposed to Prenatal Hypoxia

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% O(2)) or hypoxic (10.5% O(2)) 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 Ca(2+) (Cav1.2) and voltage‐gated K(+) channel currents and decreased calcium sensitive to the large‐conductance Ca(2+)‐activated K(+) channels. Protein expression of the L‐type voltage‐gated Ca(2+) α1C subunit, large‐conductance calcium‐activated K(+) channel (β1, not α subunits), and voltage‐gated K(+) channel (K(V)2.1, not K(V)1.5 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.