Vasoconstrictor Responses of Arteries, Veins and Microvessels from the Newborn Pulmonary Circulation † 1692

Background: There is considerable evidence that in the perinatal circulation, pulmonary veins (PV), as well as pulmonary arteries (PA), are an important site of action of vascular mediators. Furthermore, resistance to blood flow is controlled at the level of the pulmonary resistance vessels(PRV), which anatomically consist of the precapillary arterioles and the prearteriolar small arteries. Although segmental differences in the responses of the pulmonary arterial, venous and microcirculations have been documented in vivo, there are limited data comparing responses of isolated PRV to those of PA and PV from the newborn pulmonary circulation. Differential responses of PA, PRV and PV to endogenous and pharmacologic vasoconstrictors may influence pulmonary vascular resistance and blood flow, ventilation-perfusion matching and fluid exchange in the lung.Objective: Compare the concentration-dependent(10^-11-10^-6 M) responses of PA, PV and PRV isolated from newborn piglets to four vasoconstrictor agents: endothelin-1 (ET-1), U46619 (a thromboxane A₂ analogue), PGF_2α, and norepinephrine (NE).Methods: PA and PV rings were mounted in organ chambers for measurement of isometric tension; PRV were cannulated and pressurized to 15 mm Hg for measurement of lumen diameter. Results: ET-1, followed by U46619, induced the most potent constrictor responses in all vessel types. PV constricted more vigorously to ET-1, U46619 and PGF_2α than did PA; constriction to NE was greater in PA than in PV. PRV were exquisitely sensitive to ET-1 and U46619, contracting to 70 ± 6 and 50 ± 3%, respectively, of baseline lumen diameter. PRV showed minimal reactivity to NE and PGF_2α. In PRV, EC₅₀ values were in the range of 1 nM, 2 nM, 10 nM and 100 nM for ET-1, U46619, NE and PGF_2α, respectively. The EC₅₀ values for U46619 were significantly lower for PV (3 nM) than for PA (10 nM). Conclusion: There are segmental differences in the vasoconstrictor responses of the newborn pulmonary vascular bed which can affect blood flow distribution and edema formation in the lung. The greater sensitivity of microvascular and venous vs. arterial segments to ET-1 and U46619 may play a role in lung liquid production in the fetus and in the pathogenesis of pulmonary hypertension and pulmonary edema in the post-natal period.