Captopril-induced increase in coronary flow: an SH-dependent effect on arachidonic acid metabolism?
The effect of captopril (80 micrograms/ml) on coronary flow in the isolated rat heart was compared with the effects of a non-sulfhydryl-converting enzyme inhibitor, ramipril (15 micrograms/ml), and of a sulfhydryl-containing compound with no converting enzyme-inhibiting properties, glutathione (112 micrograms/ml). Drug concentrations were equipotent in their effect on angiotensin I pressor response and equimolar with respect to the sulfhydryl group. Cyclooxygenase products or their stable metabolites (TXB2, 6-keto-PGF1 alpha and PGE2) were measured in the coronary effluent. Furthermore, the effect of mepacrin (1 microM), indomethacin (1 microM), and FPL 55712 (10 microM) on the changes in coronary flow induced by captopril was studied. Both captopril- and glutathione-treated hearts showed a significant increase in coronary flow already after 5 min treatment. After 60 min treatment, coronary flow was further increased to 185 +/- 9% for captopril-treated hearts and to 210 +/- 11% for glutathione-treated hearts when compared to saline treatment. Ramipril treatment resulted in a slower increase in coronary flow, which was significant after 20 min treatment. After 60 min treatment, this increase was 122 +/- 3% when compared to saline-treated hearts. This effect of ramipril was associated with a significant increase in 6-keto-PGF1 alpha overflow when compared to saline-treated hearts. Captopril and glutathione had no significant effect on overflow of the measured cyclooxygenase products. The effect of captopril and glutathione on coronary flow appeared to be dose dependent in an equimolar range. Simultaneous mepacrin treatment diminished the effect of captopril on coronary flow; indomethacin had no effect, and FPL 55712 potentiated the effect of captopril.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D002867:Chromones / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D005978:Glutathione / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011796:Quinacrine / Q000494:pharmacology; D017257:Ramipril; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D001095:Arachidonic Acids; D001643:Bridged Bicyclo Compounds; D002867:Chromones; D013438:Sulfhydryl Compounds; D016718:Arachidonic Acid; C006312:FPL 55712; D002216:Captopril; D005978:Glutathione; D011796:Quinacrine; D017257:Ramipril; D007213:Indomethacin