Reactive oxygen species alter contractile properties of pulmonary arterial smooth muscle.
Reactive oxygen species alter pulmonary arterial vascular tone and cause changes in pulmonary vascular resistance. The objective of this investigation was to determine direct effects of oxygen radicals on the contractile properties of pulmonary arterial smooth muscle. Isolated pulmonary arterial rings from Sprague-Dawley rats were placed in tissue baths containing Earle's balanced salt solution (gassed with 95% O2 - 5% CO2, 37 degrees C, pH 7.4). Vessels were contracted with 80 mM KCl to establish maximum active force production (Po). All other responses were normalized as percentages of Po for comparative purposes. Reactive oxygen metabolites were generated enzymatically with either the xanthine oxidase (XO) reaction or the glucose oxidase (GO) reaction, or hydrogen peroxide (H2O2) was added directly to the muscle bath. Exposure to XO, GO, or to H2O2 resulted in a contractile response that was sustained during the 30-min exposure period. The muscle fully relaxed following removal of the reactive oxygen species. Resting tension remained unchanged throughout the experimental period, suggesting no functional change in membrane potential. The contractile response was dose dependent and was not prevented by either cyclooxygenase or lipoxygenase inhibition, or by removal of the endothelium. Pretreatment of vessels with superoxide dismutase (SOD) partially blocked the XO-induced contraction, while mannitol or deferoxamine had no effect on the response to XO. However, pretreatment with catalase (CAT) completely blocked the XO-induced contraction. These data suggest that superoxide ions and hydrogen peroxide are the major causative agents. Following O2-radical exposure, vessels showed a decrease in contractile responsiveness to 80 mM KCl (recovery response), suggesting damage to the smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Rhoades
R A
RA
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202.
Packer
C S
CS
Roepke
D A
DA
Jin
N
N
Meiss
R A
RA
D000818:Animals; D016166:Free Radical Scavengers; D005609:Free Radicals; D066298:In Vitro Techniques; D007537:Isometric Contraction; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D016166:Free Radical Scavengers; D005609:Free Radicals; D011189:Potassium Chloride; D010100:Oxygen; D009638:Norepinephrine