title: Chronic hypoxia decreases arterial and venous compliance in isolated perfused rat lungs: an effect that is reversed by exogenous L-arginine.
abstract: Chronic hypoxia (CH)-induced pulmonary hypertension is characterized by vasoconstriction and vascular remodeling, leading to right ventricular dysfunction. Given the role of arterial compliance (C(a)) in right ventricular work, a decrease in C(a) would add to right ventricular work. Nitric oxide (NO) is a potent vasodilator made by NO synthases from L-arginine (L-Arg). However, little is known of the effect of L-Arg on vascular compliance (C(v)) in the lung. We hypothesized that exposure to CH would decrease C(a) and that this effect would be reversed by exogenous L-Arg. Sprague-Dawley rats were exposed to either normoxia or CH for 14 days; the lungs were then isolated and perfused. Vascular occlusions were performed and modeled using a three-compliance, two-resistor model. Pressure-flow curves were generated, and a distensible vessel model was used to estimate distensibility and a vascular resistance parameter (R(0)). Hypoxia resulted in the expected increase in arterial resistance (R(a)) as well as a decrease in both C(a) and C(v). L-Arg had little effect on R(a), C(a), or C(v) in isolated lungs from normoxic animals. L-Arg decreased R(a) in lungs from CH rats and redistributed compliance to approximately that found in normoxic lungs. CH increased R(0), and L-Arg reversed this increase in R(0). L-Arg increased exhaled NO, and inhibition of L-Arg uptake attenuated the L-Arg-induced increase in exhaled NO. These data demonstrate that the CH-induced decrease in C(a) was reversed by L-Arg, suggesting that L-Arg may improve CH-induced right ventricular dysfunction.
authors.affiliation: Pulmonary Hypertension Group, Center for Perinatal Research, Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.forename: Bernadette
authors.initials: B
authors.lastname: Chen
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Calvert
authors.forename: Louis G
authors.initials: LG
authors.lastname: Chicoine
authors.forename: Yusen
authors.initials: Y
authors.lastname: Liu
authors.forename: Leif D
authors.initials: LD
authors.lastname: Nelin
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D002956:Citrulline / Q000494:pharmacology; D003187:Compliance; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008168:Lung / Q000098:blood supply* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010477:Perfusion; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011667:Pulmonary Veins / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D018497:Ventricular Dysfunction, Right / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase