Perinatal hypoxia increases KCNQ channel activity in adult rats

Abstract

Hypoxic stress at birth is linked with increased susceptibility to various diseases in adulthood. Perinatal hypoxia causes irreversible changes of the pulmonary vascular bed, some of which are more expressed in females. KCNQ (subgroup of voltage gated K+) channels have been suggested to play a role in pulmonary vascular reactivity. We hypothesized that perinatal hypoxia alters KCNQ channel activity in adulthood.Rats of the perinatal hypoxic group (PH) were born in a normobaric hypoxic chamber (FiO2 0.12; one week before the delivery) and kept in the chamber for one week after birth. Then they were raised in atmospheric air. Normoxic controls (N) were born and kept in room air. Both groups were divided according to gender and studied at the age of 20 weeks. We measured changes in perfusion pressure in isolated, saline‐perfused lungs. Dose‐response to a specific KCNQ channel inhibitor linopiridine (0.5–16 μM) was tested.In contrast to males, PH females have increased basal perfusion pressure and increased reactivity to K+ than N females. PH rats of both sexes are more sensitive to linopirdine. The increase in perfusion pressure in response to the highest linopiridine dose was 10.2 ± 1.6 mmHg in the PH group and only 5.0 ± 0.8 mmHg in the N group.Exposure to hypoxia in perinatal period increases KCNQ channel activity in adult rats.Supported by Cardiovascular Research Center MSMT 1M 0510 and Czech Science Foundation 305/08/0108.