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Köppel, H; Gasser, R; Klein, W; Holzmann, S.
ACE inhibitors with SH groups have no effect of ATP-dependent K channels--a dissertation
Acta Med Austriaca. 1996; 23(3):109-112
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Leading authors Med Uni Graz: Köppel Herwig
Co-authors Med Uni Graz: Gasser Robert
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Abstract:: ACE-inhibitors are used in the treatment of hypertension, and ischemic heart disease, chronic heart failure, cardiomyopathy and diabetic nephropathy. The effect of the ACE inhibitors is mainly due to the inhibition of the angiotensin converting-enzyme, but they also potentiate the effect of bradykinine. Sargent et al. have indicated, that SH-containing ACE-inhibitors show an effect on KATP-channel open probability in vascular smooth muscle. In our experiments, we used isolated bovine coronary arteries and guinea pig aortas, which were cut transversally and brought into Normal-Tyrode-solution. The vessels were precontracted with phenylephrine or U 46619, and after that a cumulative dose of the SH-containing ACE-inhibitors Captopril or Zofenopril was added to obtain a relaxation curve. In a second series we blocked the KATP-channels with glibenclamide to see if the relaxation could be attenuated. In bovine coronary arteries the relaxing effect of Captopril could not be attenuated by glibenclamide, a specific blocker of KATP-channels of vascular smooth muscle. In the guinea pig aorta, the relaxing effect of Zofenopril was also not effected by glibenclamide. The concentrations of Zofenopril were between 10(-7) and 10(-4) mol/l; the maximal effect could be seen at a concentration of 10(-5) mol/l. Experiments with the non SH-containing ACE-inhibitor Enalapril did also not show any statistically significant difference between the 2 groups of series. We conclude, that, in contrast to Sargent's conclusions, there is little or no effect on KATP-channels due to the presence of SH-groups.
Find related publications in this database (using NLM MeSH Indexing): Adenosine Triphosphate - metabolism; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals - pharmacology; Captopril - analogs and derivatives; Cattle - analogs and derivatives; Coronary Vessels - drug effects; Culture Techniques - drug effects; Glyburide - pharmacology; Guinea Pigs - pharmacology; Muscle, Smooth, Vascular - drug effects; Potassium Channels - drug effects; Structure-Activity Relationship - drug effects; Vasoconstriction - drug effects; Vasodilation - drug effects
Find related publications in this database (Keywords): ACE-Inhibitors; Zofenopril; Captopril; Enalapril; K-ATP-Channels; Glibenclamide