Tyrosine phosphorylation of Kv1.5 is upregulated in intrauterine growth retardation rats with exaggerated pulmonary hypertension
نویسندگان
چکیده
Intrauterine growth retardation (IUGR) is associated with the development of adult-onset diseases, including pulmonary hypertension. However, the underlying mechanism of the early nutritional insult that results in pulmonary vascular dysfunction later in life is not fully understood. Here, we investigated the role of tyrosine phosphorylation of voltage-gated potassium channel 1.5 (Kv1.5) in this prenatal event that results in exaggerated adult vascular dysfunction. A rat model of chronic hypoxia (2 weeks of hypoxia at 12 weeks old) following IUGR was used to investigate the physiological and structural effect of intrauterine malnutrition on the pulmonary artery by evaluating pulmonary artery systolic pressure and vascular diameter in male rats. Kv1.5 expression and tyrosine phosphorylation in pulmonary artery smooth muscle cells (PASMCs) were determined. We found that IUGR increased mean pulmonary artery pressure and resulted in thicker pulmonary artery smooth muscle layer in 14-week-old rats after 2 weeks of hypoxia, while no difference was observed in normoxia groups. In the PASMCs of IUGR-hypoxia rats, Kv1.5 mRNA and protein expression decreased while that of tyrosine-phosphorylated Kv1.5 significantly increased. These results demonstrate that IUGR leads to exaggerated chronic hypoxia pulmonary arterial hypertension (CH-PAH) in association with decreased Kv1.5 expression in PASMCs. This phenomenon may be mediated by increased tyrosine phosphorylation of Kv1.5 in PASMCs and it provides new insight into the prevention and treatment of IUGR-related CH-PAH.
منابع مشابه
Decreased Kv1.5 expression in intrauterine growth retardation rats with exaggerated pulmonary hypertension.
Chronic hypoxia pulmonary hypertension (CH-PHT) in adulthood is likely to be of fetal origin following intrauterine growth retardation (IUGR). Oxygen (O₂)-sensitive voltage-gated potassium channels (Kv channels) in resistance pulmonary artery smooth muscle cells (PASMCs) play an important role in scaling pulmonary artery (PA) pressure. Expression and functional changes of Kv channels are determ...
متن کامل1 Decreased Kv 1 . 5 expression in intrauterine growth retardation rats with 2 exaggerated pulmonary hypertension 3
18 Chronic hypoxia pulmonary hypertension (CH-PHT) in adulthood is likely to be of fetal 19 origin following intrauterine growth retardation (IUGR). Oxygen (O2)-sensitive voltage20 gated potassium channels (Kv channels) in resistance pulmonary artery smooth muscle 21 cells (PASMCs) play an important role in scaling pulmonary artery pressure. Expression 22 and functional changes of Kv channels a...
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