Vascular collagen affects reactivity of hypertensive pulmonary arteries of the rat.

We studied the role of vascular collagen on the responsiveness of isolated pulmonary arteries to vasoactive agonists. Dose-response curves to prostaglandin F2 alpha, (PGF2 alpha), angiotensin II (ANG II), and norepinephrine (NE) and responses to a depolarizing concentration of KCl were obtained on rings of pulmonary artery from normal rats, chronically hypoxic (10% O2 for 10 days) rats, and chronically hypoxic rats treated with cis-4-hydroxy-L-proline (cHyp), an agent that blocks collagen accumulation. Treatment with this agent prevented the rise in pulmonary blood pressure normally seen during hypoxia. Collagen content was twice normal in hypoxic vessels and was significantly reduced in vessels from cHyp-treated hypoxic rats. There was no change in reactivity to PGF2 alpha, but reactivity to ANG II, NE, and KCl was decreased in vessels from hypoxic rats. cHyp treatment completely restored reactivity to NE and KCl and partially restored reactivity to ANG II. The changes in contractility could be a response to the lower blood pressure. Another explanation is that collagen deposited in hypertensive pulmonary arteries may impair reactivity to some constrictor agonists.