Pulmonary endothelium dependent vasodilation emerges after birth in mice.

At birth, with the first breath, pulmonary vessels undergo profound adaptive processes. A failure in the ability of pulmonary vessels to adapt at birth results in persistent pulmonary hypertension of the new born. The mechanisms regulating pulmonary adaptation at birth are still unclear. Progress in this area is slow, not least because genetically modified mice have not yet been used to address questions in this area of research, principally because pulmonary vessels in new born mice are very small making the study of dilator response in vitro difficult. In the current study we have used precision cut lung slices to characterise the functional vasomotor changes in lung vessels of new born mice (1-4 days old), 8-15 day old mice or adult mice. The internal luminal area of pulmonary artery and airways was measured digitally. Vasoconstriction and vasodilatation were expressed as the percentage change in internal luminal area compared with the control area. The thromboxane A(2) mimetic U-46619 (3x10(-7) M) caused a significant vasoconstriction in vessels of all groups. However, acetylcholine (3x10(-5) M) induced arterial dilation only in the 8-15 days, and adult groups. By contrast, sodium nitroprusside, which acts independently of the endothelium, was an effective vasodilator in lung vessels from neonates. These data are the first to characterise the development of endothelium dependent vasodilatation in lung after birth in mice. This approach can be used with genetically modified mice, which is important to further our understanding of the physiology in this area.