Nitrogen oxide blockade does not aggravate the endothelin-1-induced myocardial ischemia and release of purine metabolites from the dog heart.
Increased intrapericardial levels of endothelin-1 (ET-1) induce myocardial ischemia and concomitant release of the purine metabolites adenosine (ADO), inosine (INO) and hypoxanthine (HXA) into the pericardial fluid. However, the potential modulatory role of nitrogen monoxide in compensating the ET-1-induced ischemic stress is not fully elucidated. The pericardial elevations of purine metabolite concentrations in the pericardial fluid after ET-1 administration (150 pmol/kg intrapericardially) were measured in the in situ dog heart with (n = 6) or without (n = 5) systemic nitrogen monoxide synthase blockade (30 mg/kg (G)-nitro-L-arginine methyl ester, followed by 6 mg/min intravenously). After control sampling, three consecutive pericardial infusate samples (ET1, ET2, ET3) were obtained for purine metabolite determinations (high-performance liquid chromatography-ultraviolet). It was found that intrapericardial ET-1 elevated the pericardial purine metabolite concentrations significantly in both groups. No significant differences were detected between the control and (G)-nitro-L-arginine methyl ester-treated groups in ischemic changes of pericardial ADOmax (+3.27 +/- 1.13 microM versus +1.84 +/- 0.56 microM), INOmax (+15.21 +/- 2.3 microM versus +12.09 +/- 4.04 microM) and HXAmax (+16.34 +/- 2.98 microM versus +17.09 +/- 5.22 microM) levels and in the maximal ST elevations (0.43 +/- 0.05 mV versus 0.61 +/- 0.08 mV). The hemodynamic variables did not change with ET-1 administration. In conclusion, systemic nitrogen monoxide synthase blockade does not aggravate the ET-1-induced acute myocardial ischemia and the release of purine metabolites, suggesting that endogenous nitrogen monoxide is not a supplementary factor to purine metabolites in this type of coronary adaptive responses.
Zima
Endre
E
Department of Cardiovascular Surgery, Semmelweis University, Budapest, Hungary. endzim@primposta.hu
Kékesi
Violetta
V
Nagy
Andrea
A
Barát
Erzsébet
E
Huszár
Eva
E
Toma
Ildikó
I
Merkely
Béla
B
Juhász-Nagy
Alexander
A
D000222:Adaptation, Physiological; D000241:Adenosine / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D019332:Endothelin-1; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D019271:Hypoxanthine / Q000378:metabolism; D007288:Inosine / Q000378:metabolism; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010496:Pericardium / Q000201:enzymology*; D011687:Purines / Q000378:metabolism*
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D011687:Purines; D019271:Hypoxanthine; D009569:Nitric Oxide; D007288:Inosine; D019001:Nitric Oxide Synthase; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester