Bradykinin Stimulates Endothelial Nitric Oxide (NO) Production by Calcium/Calmodulin- Dependent NO Synthase

• Published in: Hypertension Research Vol. 16; no. 2; pp. 131 - 137
• Main Authors: Emori, Toshiaki, Hirata, Yukio, Kanno, Kazuo, Marumo, Fumiaki
• Format: Journal Article
• Language: English
• Published: The Japanese Society of Hypertension 1993
• Subjects: bradykinin; Ca2; calmodulin; endothelium; nitric oxide
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1291/hypres.16.131

The cellular mechanism by which bradykinin induces nitric oxide (NO) formation was studied in cultured bovine endothelial cells. The basal release of nitrate/nitrite (NOx) from endothelial cells increased linearly during one-min incubation and reached plateau levels thereafter. Bradykinin dose-dependently and similarly stimulated NOx release and cyclic GMP production, both of which were abolished by NG-monomethyl L-arginine. D-Arg-[Hyp3, Thio5′8, D-Phe7]-bradykinin (B2-antagonist), but not Leu8-des Arg9-bradykinin (B1-antagonist), inhibited bradykinin-induced production of both NOx and cyclic GMP. Removal of extracellular Ca2+ by EGTA failed to affect bradykinin-induced NOx and cyclic GMP production, whereas intracellular Ca2+ release inhibitor (TMB-8) completely abolished NOx and cyclic GMP production stimulated by bradykinin. A relatively selective calmodulin inhibitor (W-7) blocked bradykinin-induced production of NOx and cyclic GMP. Our data suggest that bradykinin stimulates B2 receptor-mediated NO formation via activation of Ca2+/calmodulin-dependent constitutive NO synthase, and that NO may function as an autocrine/paracrine factor in endothelial cells. (Hypertens Res 1993; 16: 131-137)