Captopril inhibits endothelin-1 secretion from endothelial cells through bradykinin.
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.
Department of Geriatric Medicine, Osaka University Medical School Japan.
N
N
Momose
K
K
Fukuo
S
S
Morimoto
T
T
Ogihara
D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D002216:Captopril / Q000494:pharmacology*; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors
D016232:Endothelins; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; C053748:B 4162; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D002216:Captopril; D001920:Bradykinin