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Rat pulmonary arterial smooth muscle myosin light chain kinase and phosphatase activities decrease with age
J Belik1, Ewa Kerc, Mary D Pato
1Department of Pediatrics, Hospital for Sick Children, Univ. of Toronto, Div. of Neonatology, Hospital for Sick Children, 555 Univ. Ave., Toronto, Ontario M5G 1X8, Canada. Jaques.Belik@SickKids.ca
Summary
Fetal pulmonary arteries show higher enzyme activity for contraction and relaxation than adults, despite lower protein levels. This suggests developmental regulation of smooth muscle function is linked to enzyme specific activity.
Area of Science:
- Pulmonary vascular research
- Smooth muscle physiology
- Developmental biology
Background:
- Fetal pulmonary artery smooth muscle exhibits reduced contraction and relaxation compared to adults.
- The underlying reasons for these developmental differences in smooth muscle function are not fully understood.
Purpose of the Study:
- To investigate age-related changes in the expression and activity of key enzymes regulating pulmonary arterial smooth muscle.
- To compare myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP) in fetal, newborn, and adult rat pulmonary arteries.
Main Methods:
- Western blot analysis was used to determine the expression levels of MLCK, MYPT, and PP1cdelta.
- Enzyme specific activities were measured and compared across different age groups.
- Responses to Rho-kinase inhibitor Y-27632 were assessed.
Main Results:
- MLCK, MYPT, and PP1cdelta protein content increased significantly with age, highest in adults.
- Specific enzyme activities of MLCK and MLCP were significantly higher in fetal tissues compared to adult.
- Fetal and newborn pulmonary arteries showed a greater relaxant response to Y-27632 than adult arteries.
Conclusions:
- Pulmonary arterial smooth muscle function is developmentally regulated, with higher specific enzyme activities in fetal life.
- Elevated MLCK and MLCP specific activities in fetal pulmonary arteries may be linked to Rho-kinase activation during lung development.
- These findings provide insight into the maturation of pulmonary vascular smooth muscle mechanics.