Concentration-dependent effects of purine/xanthine oxidase on release of 6-keto-PGF1 alpha and contractile function of isolated guinea pig hearts: response to "ischemic" conditions followed by reperfusion.
This study was designed to demonstrate the concentration-dependent effects of an exogenous free-radical-generating system on the functional characteristics of isolated perfused guinea pig hearts under normal conditions and in response to conditions associated with ischemia followed by reperfusion. Purine (0.0115-0.23 mM) and xanthine oxidase (0.05-1.0 U/L) were added to normal Tyrode's solution and perfused for 40 min. Purine (0.0575-0.23 mM)/xanthine oxidase (0.25-1.0 U/L) produced a decline in contractile force that ranged from 59 to 44% of initial values (p less than 0.05). Although all concentrations of the free-radical-generating system enhanced resting tension when compared to control, this increase was only significant in the presence of purine (0.0115 and 0.0575 mM)/xanthine oxidase (0.05 and 0.25 U/L), following a 20-40 min perfusion period (p less than 0.05). Significant correlations were found between the concentration of the free-radical-generating system and the depression in contractile force (p less than 0.05), as well as between the loss of force and the enhancement of resting tension (p less than 0.002) in the presence of all concentrations of purine/xanthine oxidase examined. Furthermore, purine/xanthine oxidase was a potent stimulus for release of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). While this release was correlated significantly with the concentration of purine/xanthine oxidase (p less than 0.001), there was no significant relationship between the decline in contractile force and the release of 6-keto-PGF1 alpha per se.(ABSTRACT TRUNCATED AT 250 WORDS)
Tsushima
R G
RG
Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada.
Moffat
M P
MP
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015425:Myocardial Reperfusion; D014969:Xanthine Oxidase / Q000494:pharmacology*
D005609:Free Radicals; D015121:6-Ketoprostaglandin F1 alpha; D014969:Xanthine Oxidase