THE VASODILATIVE EFFECT OF ACE-INHIBITORS CONTAINING SH-GROUPS IS NOTMEDIATED BY KATP-CHANNELS - A THESIS

ACE-inhibitors are used in the treatment of hypertension, and ischemic heart disease, chronic heart failure, cardiomyopathy and diabetic nep hropathy. The effect of the ACE inhibitors is mainly due to the inhibi tion of the angiotensin converting-enzyme, but they also potentiate th e effect of bradykinine. Sargent et al. have indicated, that SH-contai ning ACE-inhibitors show an effect on K-ATP-channel open probability i n 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 precontracte d with phenylephrine or U 46619, and after that a cumulative dose of t he SH-containing ACE-inhibitors Captopril or Zofenopril was added to o btain a relaxation curve. In a second series we blocked the K-ATP-chan nels 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 K-ATP-channels of vascular smooth muscle. In the guinea pig aorta, the relaxing effec t of Zofenopril was also not effected by glibenclamide. The concentrat ions of Zofenopril were between 10(-7) and 10(-4) mol/l; the maximal e ffect could be seen at a concentration of 10(-5) mol/l, Experiments wi th 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 littl e or no effect on K-ATP-channels due to the presence of SH-groups.