Effects of peroxynitrite on pig coronary artery smooth muscle.
We examined the effects of peroxynitrite pretreatment of pig coronary arteries on their sarcoplasmic reticulum (SR) Ca(2+) pump function. Pretreating rings from de-endothelialized arteries with peroxynitrite, followed by a wash to remove this agent, led to a decrease in the force of contraction produced in response to the SR Ca(2+) pump inhibitor cyclopiazonic acid (CPA, IC(50) = 87 +/- 6 microM). Inclusion of catalase and superoxide dismutase with the peroxynitrite did not alter its effect indicating that the inhibition was produced by peroxynitrite. Contractions produced by 30 mM KCl were not affected by up to 250 microM peroxynitrite. Smooth muscle cells cultured from this artery gave a transient increase in cytosolic Ca(2+) in response to CPA. Treating the cells with peroxynitrite inhibited this increase. Treating the SR-enriched isolated subcellular membrane fraction with peroxynitrite produced an inhibition of the ATP-dependent azide-insensitive oxalate-stimulated Ca(2+) uptake. Thus, peroxynitrite damages the SR Ca(2+)pump in the coronary artery, and this inhibition appears to lead to an inability of the arteries to respond to CPA. Thus, peroxynitrite produced from superoxide and NO in the arteries may compromise regulation of coronary tone which requires mobilization of Ca(2+) from the SR.
Walia
Mandeep
M
Department of Medicine, HSC 4N41 McMaster University, 1200 Main Street West, Hamilton, Ont., Canada L8N3Z5.
Samson
Sue E
SE
Schmidt
Tracey
T
Best
Kelly
K
Kwan
Chiu Yin
CY
Grover
Ashok K
AK
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000187:drug effects / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism* / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D034421:Sus scrofa; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D007211:Indoles; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid