Altered reactivity of pulmonary vessels in postobstructive pulmonary vasculopathy

Chronic ligation of one pulmonary artery results in pulmonary vascular remodelling and bronchial angiogenesis, known as postobstructive pulmonary vasculopathy (POPV). In previous studies of POPV, we found that responses of pulmonary arteries to 5-HT and of veins to histamine were markedly increased, but the role of putative factors, such as structure, endothelial modulation and alterations in receptors remains unknown. First, we examined the role of these mechanisms in the differential responses of pulmonary arteries and veins of normal guinea pigs to histamine and 5-HT, using a novel lung explant technique. We found that veins contracted more to both agonists than arteries, and that H2 receptors were responsible for the differential contractile responses of pulmonary arteries and veins to histamine, whereas endothelium-derived vasoactive substances (nitric oxide and prostacyclin) were responsible for their differential contractile responses to 5-HT. We also investigated relaxation responses, and found that endothelial-dependent NO-mediated relaxation was greater in pulmonary arteries than veins, and that acetylcholine-induced NO-mediated relaxation was reduced by the simultaneous production of cyclooxygenase-derived vasoconstrictors.Second, we did experiments in guinea pigs with POPV, and found that the maximal contractions of pulmonary arteries to 5-HT and of veins to histamine were increased compared with controls, and that the augmented responses were not due to endothelial dysfunction nor to structural alterations, but probably to changes in the smooth muscle proper. To ascertain responses to endothelin (ET), and the role of altered receptors, specifically ET receptors, in POPV, we produced the model in rats: we found that contractions to ET-1 and ET-3 were increased and that relaxation to ET-1 was reduced significantly only in the pulmonary arteries with POPV compared with controls; these findings were attributed, using receptor binding studies, to an augmented proportion of ETA over ETB receptors.We conclude that the differential contractile responses of normal pulmonary arteries and veins to histamine and 5-HT, and the altered vascular responses to these amines and to ETs in POPV, are due primarily to differences in receptors or in endothelial modulation, rather than to disparities in vascular structure