Peroxynitrite and nitric oxide differ in their effects on pig coronary artery smooth muscle.
Peroxynitrite generated in arteries from superoxide and nitric oxide (NO) may damage their function. Here, we compare the effects of peroxynitrite and peroxynitrite/NO-generating agents SIN-1 (3-morpholinosydnonimine hydrochloride), SNAP (S-nitroso-N-acetyl-penicillamine), SNP (sodium nitroprusside), and NONOate (spermine NONOate) on pig coronary artery. Deendothelialized artery rings were pretreated with these agents and then washed before examining their contractility. Pretreatment with all agents (200 microM) results in a decrease in the force of contraction in response to the sarco(endo)plasmic Ca(2+) (SERCA) pump inhibitor cyclopiazonic acid (CPA): SNAP > NONOate > or = peroxynitrite > or = SIN-1 > SNP. Pretreatment with SNAP, NONOate, or SIN-1 also inhibits the force of contraction produced with 30 mM KCl, with SNAP being the most potent. Including catalase plus superoxide dismutase (SOD) during the preincubation has no effect. Including an NO scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide] or a guanylate cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) partially protects against SNAP. Pretreatment of cultured cells with peroxynitrite, but not with SNAP, inhibits the Ca(2+) transients produced in response to CPA. Pretreating isolated membrane vesicles with peroxynitrite inhibits the Ca(2+) uptake due to the SERCA pump, with all the other agents being less effective. Thus peroxynitrite and NO both inhibit the CPA-induced contractions in deendothelialized artery rings, peroxynitrite by damage to the SERCA pump and NO possibly by a step downstream from the increase in cytosolic Ca(2+).
Walia
Mandeep
M
Department of Medicine, HSC 4N41 McMaster University, Hamilton, Ontario, Canada L8N3Z5.
Samson
Sue E
SE
Schmidt
Tracey
T
Best
Kelly
K
Whittington
Melinda
M
Kwan
Chiu Yin
CY
Grover
Ashok K
AK
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D030421:Peroxynitrous Acid / Q000378:metabolism* / Q000494:pharmacology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013552:Swine; D022161:Transport Vesicles / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D020030:Nitric Oxide Donors; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases