EDRF does not mediate coronary vasodilation secondary to simulated ischemia : A study on KATP channels and Nω-nitro-L-arginine on coronary perfusion pressure in isolated Langendorff-perfused guinea-pig hearts

• Published in: Cardiovascular drugs and therapy 1998-07, Vol.12 (3), p.279-284
• Main Authors: GASSER, R, KÖPPEL, H, BRUSSEE, H, GRISOLD, M, HOLZMANN, S, KLEIN, W
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - pharmacology; Animals; Biological and medical sciences; Cardiology. Vascular system; Coronary Circulation - drug effects; Coronary heart disease; Enzyme Inhibitors - therapeutic use; Glyburide - pharmacology; Guinea Pigs; Heart; In Vitro Techniques; Medical sciences; Myocardial Ischemia - chemically induced; Myocardial Ischemia - physiopathology; Nitric Oxide - physiology; Nitroarginine - therapeutic use; Nitrogen - pharmacology; Perfusion; Potassium Channels - physiology; Vasodilation - physiology
• ISSN: 0920-3206; 1573-7241

Several authors have alluded to the possible involvement of EDRF (NO) in ischemia-induced coronary artery dilation. Alternatively, it has been suggested that opening of ATP-dependent K channels could play a key role in this context. We studied the effects of sulfonylureas and NG-nitro-L-arginine (LNNA), a specific inhibitor of endothelial NO (EDRF) synthesis, on ischemia-induced coronary vasodilation in isolated Langendorff-perfused guinea pig hearts arrested with 15 mM KCl in normal Tyrode, and isolated pig coronary arteries precontracted with 43 mM KCl. In Isolated Langerdorff-perfused guinea pig heart, when hypoxia was simulated by switching 100% O2 in the perfusate to 100% N2, coronary perfusion pressure (CPP) fell from 90 cm H2O by 45 +/- 5 cm H2O. In the presence of LNNA, a specific inhibitor of NO synthetase in endothelial cells, CPP dropped by 44 +/- 6 cm H2O (n = 6; +/- SEM, no statistically significant). On biochemical simulation of ischemia (addition of iodoacetate [IAA]), CPP dropped 40 +/- 6 cm H2O, and in experiments performed under the same conditions but in the presence of LNNA, CPP dropped by 38 +/- 5 cm H2O (n = 6; +/- SEM; not statistically significant). When ischemia was simulated metabolically by equimolar replacement of 10 mM glucose with 2-deoxyglucose (DOG), an inhibitor of glycolysis CPP decreased by 24 +/- 1 cm H2O (n = 6; +/- SEM) after 15 minutes. This fall in CPP was almost prevented by 20 microM glibenclamide, whereas in the presence of 20 microM LNNA the DOG-induced decrease in CPP was not significantly inhibited, and CPP decreased by 22 +/- 2.6 cm H2O (n = 6; +/- SEM). In isolated pig coronary artery rings, maximal tension, achieved by depolarizing the smooth muscle cells by 43 mM KCl, decreased by 37 +/- 7% upon simulated hypoxia by replacing 100% O2 with 100% N2 in the perfusate (n = 6; +/- SEM) in arteries with intact endothelium. In arteries without endothelium, maximal tension also dropped by 35 +/- 6% (not statistically significant). In the same experiments the decrease in tension could be largely inhibited in the presence of 50 microM glibenclamide. Our results clearly show that in isolated perfused guinea pig hearts, as well as in isolated pig coronary arteries, EDRF does not play a decisive role in the coronary dilatory response to hypoxia and ischemia.