Nitric oxide-induced cardioprotection in cultured rat ventricular myocytes.
The aim of this study was to investigate the role of nitric oxide (NO) in a cellular model of early preconditioning (PC) in cultured neonatal rat ventricular myocytes. Cardiomyocytes "preconditioned" with 90 min of stimulated ischemia (SI) followed by 30 min reoxygenation in normal culture conditions were protected against subsequent 6 h of SI. PC was blocked by N(G)-monomethyl-L-arginine monoacetate but not by dexamethasone pretreatment. Inducible nitric oxide synthase (NOS) protein expression was not detected during PC ischemia. Pretreatment (90 min) with the NO donor S-nitroso-N-acetyl-L,L-penicillamine (SNAP) mimicked PC, resulting in significant protection. SNAP-triggered protection was completely abolished by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) but was unaffected by chelerythrine or the presence of glibenclamide and 5-hydroxydecanoate. With the use of RIA, SNAP treatment increased cGMP levels, which were blocked by ODQ. Hence, NO is implicated as a trigger in this model of early PC via activation of a constitutive NOS isoform. After exposure to SNAP, the mechanism of cardioprotection is cGMP dependent but independent of protein kinase C or ATP-sensitive K(+) channels. This differs from the proposed mechanism of NO-induced cardioprotection in late PC.
Rakhit
R D
RD
Department of Cardiology, St. Thomas' Hospital, Kings College, London SE1 7EH, United Kingdom.
Edwards
R J
RJ
Mockridge
J W
JW
Baydoun
A R
AR
Wyatt
A W
AW
Mann
G E
GE
Marber
M S
MS
D000470:Alkaloids; D000818:Animals; D000831:Animals, Newborn; D000890:Anti-Infective Agents / Q000494:pharmacology; D053119:Benzophenanthridines; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D019194:Ischemic Preconditioning; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010069:Oxadiazoles / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; C117236:2-methoxy-5-hexadecenoic acid; D000470:Alkaloids; D000890:Anti-Infective Agents; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D010069:Oxadiazoles; D010617:Phenanthridines; D015221:Potassium Channels; D011810:Quinoxalines; C110881:S-nitro-N-acetylpenicillamine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003907:Dexamethasone; C016299:chelerythrine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D011493:Protein Kinase C; D010396:Penicillamine; D006152:Cyclic GMP; D005905:Glyburide