Glutathione S-transferase (GST) independent formation of nitric oxide from nitroglycerin in pig coronary artery.

The role of nitric oxide and guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in the endothelium-dependent relaxation of the porcine coronary artery to bradykinin was investigated by comparing relaxation and cGMP accumulation in the presence or absence of NG-monomethyl-L-arginine (L-NMMA) and methylene blue. Rings were treated with indomethacin to eliminate the effects of prostaglandins. Relaxation to bradykinin of rings contracted with the thromboxane A2 mimetic U-46619 was not affected by L-NMMA and was only minimally inhibited by methylene blue. Rings contracted with elevated potassium (25 mM) also relaxed completely to bradykinin. However, L-NMMA or methylene blue effectively inhibited relaxation to bradykinin in rings contracted with potassium. cGMP accumulation was stimulated by bradykinin and inhibited by L-NMMA or methylene blue in rings contracted with either U-46619 or potassium. These results suggest that in the absence of nitric oxide-induced cGMP accumulation, a nonprostanoid mechanism exists that is capable of completely relaxing U-46619-contracted coronary artery. This mechanism is either inhibited in or unable to relax potassium-contracted rings. These results also demonstrate that nitric oxide mediates the bradykinin-induced cGMP accumulation that is largely responsible for the relaxation during contraction with potassium.

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

AJP Cell Physiology ◽

10.1152/ajpcell.00405.2002 ◽

2003 ◽

Vol 284 (3) ◽

pp. C649-C657 ◽

Cited By ~ 18

Author(s):

Mandeep Walia ◽

Sue E. Samson ◽

Tracey Schmidt ◽

Kelly Best ◽

Melinda Whittington ◽

...

Keyword(s):

Nitric Oxide ◽

Coronary Artery ◽

Cultured Cells ◽

Cyclopiazonic Acid ◽

Membrane Vesicles ◽

Force Of Contraction ◽

Serca Pump ◽

Pig Coronary Artery ◽

Spermine Nonoate ◽

Isolated Membrane Vesicles

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 μM) results in a decrease in the force of contraction in response to the sarco(endo)plasmic Ca2+ (SERCA) pump inhibitor cyclopiazonic acid (CPA): SNAP > NONOate ≥ peroxynitrite ≥ 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 (1 H-[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 deendothelialized 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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