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Pulmonary arterioles from rats with congenital diaphragmatic hernias are hypoplastic but not hyperresponsive
M Au-Fliegner1, S Salami, J R Gosche
1Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.
Insights
Congenital diaphragmatic hernia (CDH) in infants causes pulmonary hypertension. This study found that despite structural changes in pulmonary arterioles in a CDH rat model, vasoconstrictor responses were not exaggerated.
Area of Science:
- Pulmonary Hypertension Research
- Vascular Biology
- Neonatal Pathology
Background:
- Infants with congenital diaphragmatic hernia (CDH) often face mortality due to pulmonary hypertension and persistent fetal circulation.
- Pulmonary vessels in CDH infants exhibit reduced cross-sectional area, increased muscle content, and abnormal arteriole muscularization.
- These vascular changes are hypothesized to lead to exaggerated vasoconstrictor responses.
Purpose of the Study:
- To investigate whether pulmonary arterioles in an animal model of CDH display exaggerated vasoconstrictor responses.
- To compare the reactivity of pulmonary arterioles from normal rats and rats with nitrofen-induced CDH.
Main Methods:
- Utilized the nitrofen-induced CDH model in rats.
- Isolated and compared third-generation pulmonary arterioles from control and CDH rats.
- Assessed responses to various vasoconstrictors including K+-induced depolarization, phenylephrine, angiotensin II, serotonin, and U46619.
Main Results:
- Pulmonary arterioles in CDH rats had a significantly smaller intraluminal diameter compared to controls (129 ± 5 µm vs. 152 ± 9 µm).
- The ratio of wall thickness to internal diameter was increased in CDH rat arterioles (0.62 ± 0.4 vs. 0.50 ± 0.5).
- No significant differences in vasoconstrictor responses were observed between control and CDH rat pulmonary arterioles.
Conclusions:
- Structural alterations in the pulmonary vasculature of CDH may not result in exaggerated vasoconstrictor responses to common stimuli.
- Findings challenge the assumption that vascular remodeling alone drives exaggerated vasoconstriction in CDH.
Background:
Infants born with congenital diaphragmatic hernias (CDH) frequently die as a result of pulmonary hypertension and persistent fetal circulation. The pulmonary vessels of infants with CDH have decreased total cross-sectional area, increased muscle content, and muscularization of intra-acinar arterioles that are normally not muscularized. These structural alterations are believed to result in exaggerated responses to normal vasoconstrictor stimuli.
Methods:
The authors used the nitrofen-induced CDH model in rats to determine whether the vasoconstrictor responses of pulmonary arterioles are exaggerated in this animal model of CDH. The authors compared the responses of isolated third-generation pulmonary arterioles from normal rats and from rats with nitrofen-induced CDH to K+-induced depolarization, phenylephrine, angiotensin II, serotonin, and the thromboxane A2 agonist, U46619.
Results:
It was found that the intraluminal diameter of third-generation pulmonary arterioles from CDH rats was significantly less than in controls (129 +/- 5 micron v 152 +/- 9 micron, respectively). In addition, the ratio of wall thickness to vessel internal diameter was increased in the third-generation pulmonary arterioles of rats with nitrofen-induced CDH (0.62 +/- 0.4 v 0.50 +/- 0.5 for controls). Responses to K+-induced depolarization, phenylephrine, angiotensin II, serotonin, and U46619, however, were not different for pulmonary arterioles from control and CDH rats.
Conclusion:
These data suggest that the structural alterations of the pulmonary vasculature observed in infants with CDH may not cause exaggerated vasoconstrictor responses to normal vasoconstrictor stimuli.