Role of sulfhydryl groups in the stimulatory effect of captopril on vascular prostacyclin synthesis.
The effect of captopril on vascular prostacyclin production was studied, evaluating which of its components--sulfhydryl (SH) group or proline--is responsible for this effect. Rat aortas were incubated with captopril (10-100 microM), 2-mercaptoethanol or proline (10 microM), and captopril plus the SH-binding reagents N-ethylmaleimide or ethacrynic acid (50 microM). Prostacyclin was measured by radioimmunoassay of 6-keto-prostaglandin F1 alpha. Captopril stimulated prostacyclin production. This effect was associated with an enhanced conversion of arachidonate to prostacyclin and was not related to bradykinin. Since 2-mercaptoethanol increased vascular prostacyclin per se and proline did not, the stimulatory effect of captopril appears to be dependent upon the SH group; in addition, both SH blockers, N-ethylmaleimide and ethacrynic acid, antagonized this effect. This study shows that captopril stimulates vascular prostacyclin synthesis directly and that the SH group plays a key role in this action. This stimulation of prostacyclin synthesis may contribute to the antihypertensive action of captopril.
Department of Pharmacology, School of Medicine, University of Chile, Santiago.
M
M
Guivernau
F
F
Armijo
R
R
Rosas
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis*; D004976:Ethacrynic Acid / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D008297:Male; D008623:Mercaptoethanol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011392:Proline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D013438:Sulfhydryl Compounds; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D008623:Mercaptoethanol; D011392:Proline; D002216:Captopril; D011464:Epoprostenol; D004976:Ethacrynic Acid; D005033:Ethylmaleimide