Captopril inhibits endothelin-1 secretion from endothelial cells through bradykinin

Hypertension. 1993 Jun;21(6 Pt 2):921-4. doi: 10.1161/01.hyp.21.6.921.


Incubation with captopril, an angiotensin I converting enzyme inhibitor, for 24 hours at concentrations up to 10(-7) M inhibited endothelin-1 secretion by endothelial cells. This inhibition of endothelin-1 secretion was reversed by coincubation with 3 x 10(-3) M NG-nitro-L-arginine, an inhibitor of nitric oxide synthesis. Furthermore, captopril enhanced the production of nitric oxide in endothelial cells, suggesting that enhancement of nitric oxide production participates in captopril-induced inhibition of endothelin-1 secretion. Moreover, in the presence of 10(-6) M D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin, a bradykinin B2 receptor antagonist, captopril did not inhibit but rather stimulated endothelin-1 secretion, whereas bradykinin inhibited endothelin-1 secretion, and this inhibition by bradykinin was reversed by coincubation with NG-nitro-L-arginine. In addition, enhancement of nitric oxide production induced by either captopril or bradykinin was inhibited by D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin. Although 10(-6) M des-Arg9-[Leu8]-bradykinin, a bradykinin B1 receptor antagonist, did not affect nitric oxide production by bradykinin, it enhanced the inhibition of endothelin-1 secretion by bradykinin. Furthermore, 10(-7) M des-Arg9-bradykinin, a bradykinin B1 receptor agonist, stimulated endothelin-1 secretion by endothelial cells. These findings suggest that angiotensin I converting enzyme inhibitor inhibits endothelin-1 secretion by the accumulation of endogenous bradykinin in endothelial cells and that the inhibition of endothelin-1 secretion by bradykinin is mediated via B2 receptors.

MeSH terms

  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Bradykinin / analogs & derivatives
  • Bradykinin / pharmacology
  • Bradykinin / physiology*
  • Captopril / pharmacology*
  • Cells, Cultured
  • Endothelins / metabolism*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Humans
  • Nitric Oxide / metabolism
  • Nitroarginine
  • Receptors, Bradykinin
  • Receptors, Neurotransmitter / antagonists & inhibitors


  • Endothelins
  • Receptors, Bradykinin
  • Receptors, Neurotransmitter
  • B 4162
  • Nitroarginine
  • Nitric Oxide
  • Arginine
  • Captopril
  • Bradykinin