Role of superoxide anion on basal and stimulated nitric oxide activity in neonatal piglet pulmonary vessels.
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.
Villamor
Eduardo
E
Department of Pediatrics, University Hospital Maastricht, Research Institute Growth and Development (GROW), University of Maastricht, P. Debyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. eiv@paed.azm.nl
Kessels
Carolina G A
CG
Fischer
Marc A J
MA
Bast
Aalt
A
de Mey
Jo G R
JG
Blanco
Carlos E
CE
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D019327:Copper Sulfate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D009126:Muscle Relaxation / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D011651:Pulmonary Artery / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D011667:Pulmonary Veins / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013481:Superoxides / Q000494:pharmacology*; D013552:Swine
D004791:Enzyme Inhibitors; D013481:Superoxides; D009569:Nitric Oxide; D004958:Estradiol; C073106:3,17-diacetoxyestra-1,3,5(10)-trien-2-carboxylic acid; D013482:Superoxide Dismutase; D019327:Copper Sulfate; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester