Role of superoxide anion on basal and stimulated nitric oxide activity in neonatal piglet pulmonary vessels

• Published in: Pediatric research Vol. 54; no. 3; pp. 372 - 381
• Main Authors: VILLAMOR, Eduardo, KESSELS, Carolina G. A, FISCHER, Marc A. J, BAST, Aalt, DE MEY, Jo G. R, BLANCO, Carlos E
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.09.2003
• Subjects: Acetylcholine - pharmacology; Animals; Animals, Newborn; Biological and medical sciences; Copper Sulfate - pharmacology; Dose-Response Relationship, Drug; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Enzyme Inhibitors - pharmacology; Estradiol - analogs & derivatives; Estradiol - pharmacology; Fundamental and applied biological sciences. Psychology; General aspects; Genetics of eukaryotes. Biological and molecular evolution; In Vitro Techniques; Liver - metabolism; Medical sciences; Molecular and cellular biology; Muscle Contraction - physiology; Muscle Relaxation - physiology; Muscle, Smooth, Vascular - metabolism; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - metabolism; Pulmonary Artery - anatomy & histology; Pulmonary Artery - drug effects; Pulmonary Artery - metabolism; Pulmonary Veins - anatomy & histology; Pulmonary Veins - drug effects; Pulmonary Veins - metabolism; Superoxide Dismutase - antagonists & inhibitors; Superoxide Dismutase - chemistry; Superoxide Dismutase - metabolism; Superoxide Dismutase - pharmacology; Superoxides - pharmacology; Swine; Pediatrics; Activity; Pig; Vertebrata; Anions; Hyperoxides; Mammalia; Pulmonary vessel; Newborn animal; Nitric oxide; Genetics; Artiodactyla; Ungulata
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1203/01.PDR.0000077481.15081.C8

The superoxide anion (O2*-) appears to be an important modulator of nitric oxide bioavailability. Enzymatic scavenging of O2*- is carried out by superoxide dismutase (SOD). The present study was designed to characterize the developmental changes on pulmonary vascular reactivity induced by 1) exogenous Cu/Zn SOD, 2) several putative SOD mimetics, and 3) endogenous SOD inhibition. We also analyzed age-related changes on pulmonary SOD activity and vascular O2*- levels. SOD (1-300 U/mL) produced endothelium-dependent relaxation of U46619-contracted intrapulmonary arteries (fourth branch) and veins from 12- to 24-h-old and 2-wk-old piglets. SOD-induced relaxation was greater in pulmonary arteries and was abolished by the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester. SOD induced a greater pulmonary artery relaxation in the 2-wk-old than in the 12- to 24-h-old piglet. SOD (100 U/mL) did not modify acetylcholine-induced relaxation in pulmonary arteries. In contrast, endogenous SOD inhibition by diethyldithiocarbamate (3 mM) impaired acetylcholine-induced relaxation in pulmonary arteries from newborn but not from 2-wk-old piglets. Total SOD activity in lung tissue did not change with postnatal age. With the use of dihydroethidium, an oxidant-sensitive fluorescent probe, we did not find significant age- or vessel-related differences in O2*- presence. From the putative SOD mimetics tested, only the metal salts MnCl2 and CuSO4 reproduced the vascular effects of SOD. In summary, SOD produces endothelium-dependent pulmonary vascular relaxation by protecting nitric oxide from destruction by O2*-. This effect was less marked in newborns than in 2-wk-old piglets. In contrast, pulmonary arteries from newborn piglets are more sensitive to the inhibition of endogenous SOD.