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Am J Physiol Cell Physiol (November 13, 2002). doi:10.1152/ajpcell.00405.2002
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Articles in PresS, published online ahead of print November 13, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00405.2002
Submitted on September 4, 2002
Accepted on November 5, 2002

Peroxynitrite and nitric oxide differ in their effects on pig coronary artery smooth muscle

Mandeep Walia1, Sue E Samson2, Tracey Schmidt2, Kelly Best1, Melinda Whittington2, Chui-Yin Kwan2, and Ashok K Grover3*

1 Department of Biology, McMaster University, Hamilton, ON, Canada
2 Department of Medicine, McMaster University, Hamilton, ON, Canada
3 Department of Medicine, McMaster University, Hamilton, ON, Canada; Department of Biology, McMaster University, Hamilton, ON, Canada

* To whom correspondence should be addressed. E-mail: groverak{at}mcmaster.ca.

Peroxynitrite generated in arteries from superoxide and 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-acetylypenicillamine), SNP (sodium nitroprusside) and NONOate (Spermine NONOate) on pig coronary artery. De-endoethelialized artery rings were pretreated with these agents and then washed before examining their contractility. The pretreatment with all the agents (200 µM) results in a decrease in the force of contraction in response to the sarco/endoplasmic Ca2+ pump (SERCA) inhibitor cyclopiazonic acid (CPA): SNAP > NONOate >= peroxynitrite >= SIN-1 > SNAP. 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 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 Ca2+ transients produced in response to CPA. Pretreating isolated membrane vesicles with peroxynitrite inhibits the Ca2+ 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 de-endothelialized artery rings - peroxynitrite by damage to the SERCA pump and NO possibly by a step downstream from the increase in cytosolic Ca2+.




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