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.
Chronic hypoxia damages peripheral pulmonary vessels and causes hypoxic pulmonary hypertension (HPH). According to our hypothesis, the release of reactive oxygen species (ROS), nitric oxide (NO) and products of their interaction contribute to the pathogenesis of HPH. Experimenting with chronic hypoxic adult male rats, we tested the effect of NO and ROS interaction. Hypoxic rats were treated solely with SOD mimetic Tempol (group T, n=6) and NO donor Molsidomine (group M, n=9) or in combination (group MT, n=6) during first 7 days of exposure to 3 weeks hypoxia (FiO2=0.1). Seven untreated hypoxic rats (group H) and seven normoxic controls (group C) were used.Pulmonary artery blood pressure (PAP), and the weight of RV, LV+S were measured. PAP was significantly decreased in group M (P<0.05) and group T (P<0.05) but not in group MT compared with group H. In all hypoxic groups the right‐to‐left heart weight ratio was significantly increased compared to group C, and groups receiving Tempol (T, MT) had significantly (P<0.01 and P<0.01 respectively) less increase in weight of RV or whole heart compared with group H.Molsidomine or Tempol added alone (but not in combination) at the beginning of exposure to chronic hypoxia reduces HPH. Tempol alone or in a combination reduces of hypoxia‐induced right heart hypertrophy.Supported by Cardiovascular Research Center MSMT 1M 0510, Grants: GACR 305/05/0672 and GAUK 7780/2007
Superoxide, nitric oxide (NO) and peroxynitrite play a pathogenetic role in the development of hypoxic pulmonary hypertension (HPH).Rats exposed to normobaric hypoxia with hypercapnia (10% O2+4.5% CO2, n=7) for 3 weeks had significantly lower (22.9 vs. 30.0 mmHg, p<0.01) PAP and right ventricle weight (RV/LV+S ratio, 34.4 vs. 54.0, p<0.0001) compared to rats exposed to hypoxia with no hypercapnia (10% O2, n=9).We tested the hypothesis that superoxide ‐ NO interaction plays role in inhibition of HPH by hypercapnia. We measured the expired amount of NO of living rats and the level of NOx in plasma by the chemiluminescent method and the plasma concentration of nitrotyrosine (a marker of peroxynitrite) by ELISA on male adult Wistar rats exposed to normobaric hypoxia ‐ 10% O2 (group H, n=6) or normobaric hypoxia ‐ 10% O2 with hypercapnia ‐ 4.5% CO2 (group H+CO2, n=6) for 4 days. Group N (n=6) were normoxic controls. The amount of expired NO (689.3 vs. 889.2 pg.min−1, p<0.05), the level of NOx in plasma (57.4 vs. 97.2 µM, p<0.01) and the plasma concentration of nitrotyrosine (7.9 vs. 9.9 µM, p<0.05) were significantly decreased in group H+CO2 compared to group H.Superoxide ‐ NO interaction plays an important role in inhibition of HPH by hypercapnia.Supported by Cardiovascular Research Centre MSMT 1M 0510 and Grant: GAUK 7780/2007
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.