Endothelin-1 enhances nitric oxide-induced cytotoxicity in vascular smooth muscle.
Prolonged incubation with 1 nmol/L interleukin-1 induced high levels of nitric oxide release and cytotoxicity in vascular smooth muscle cells. NG-Monomethyl-L-arginine, an inhibitor of nitric oxide synthesis, inhibited interleukin-1-induced cytotoxicity at a concentration of 3 mmol/L. Furthermore, prolonged incubation with 0.1 mmol/L sodium nitroprusside, a nitric oxide donor, also induced cytotoxicity. On the other hand, endothelin-1 at concentrations from 10(-10) to 10(-7) mol/L induced a concentration-dependent enhancement of cytotoxicity induced by interleukin-1. However, endothelin-1 did not affect interleukin-1-induced nitric oxide production. Coculture study of vascular smooth muscle cells and endothelial cells without direct cell contact revealed that incubation for 72 hours with interleukin-1 induced high levels of nitric oxide release from cocultured vascular smooth muscle cells to the same degree as release from vascular smooth muscle cells alone. However, interleukin-1-induced cytotoxicity was more enhanced in cocultured vascular smooth muscle cells than in vascular smooth muscle cells alone. Furthermore, coincubation with 20 nmol/L BQ-485, an antagonist of one type of endothelin receptor (ETA), prevented the enhancement of interleukin-1-induced cytotoxicity in cocultured vascular smooth muscle cells. These findings suggest that endothelin-1 secreted from endothelial cells may enhance nitric oxide-induced cytotoxicity by means of the ETA receptor in vascular smooth muscle cells.
Nakahashi
T
T
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Fukuo
K
K
Inoue
T
T
Morimoto
S
S
Hata
S
S
Yano
M
M
Ogihara
T
T
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D016232:Endothelins / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007930:Leucine / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D016232:Endothelins; D007375:Interleukin-1; D009599:Nitroprusside; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D007930:Leucine