Bradykinin stimulates the production of cyclic GMP via activation of B2 kinin receptors in cultured porcine aortic endothelial cells.
The production of endothelium-derived relaxing factor(s) in response to kinins was investigated in cultured porcine aortic endothelial cells. The production was estimated by the measurement of the accumulation of cyclic GMP, a response which can be attributed to activation of the soluble guanylate cyclase of the endothelial cells by endothelium-derived relaxing factor(s). Bradykinin increased markedly the levels of cyclic GMP in endothelial cells without affecting those of cyclic AMP. The bradykinin-stimulated production of cyclic GMP was transient and concentration-dependent. Kallidin (an agonist at B2-kinin receptors) but not des-Arg9 bradykinin and des-Arg10 kallidin (agonists at B1 kinin receptors) also increased, in a concentration-dependent manner, the content of cyclic GMP. The B2 kinin receptor antagonist, D-Arg0 [Hyp3, D-Phe7]bradykinin but not the B1 kinin receptor antagonists Leu8-des-Arg9 bradykinin and Leu9-des-Arg10 kallidin inhibited the production of cyclic GMP upon stimulation of the endothelial cells with either bradykinin or kallidin. Both the basal and kinin (bradykinin and kallidin)-stimulated productions of cyclic GMP were reduced by hemoglobin and potentiated by superoxide dismutase. Methylene blue also reduced kinin-stimulated production of cyclic GMP. These findings suggest that cultured porcine aortic endothelial cells possess B2 kinin receptors which are associated with the production and/or release of endothelium-derived relaxing factor(s). The endothelium-derived relaxing factor(s) produced in turn enhances the activity of soluble guanylate cyclase and induces the accumulation of cyclic GMP.
Schini
V B
VB
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota.
Boulanger
C
C
Regoli
D
D
Vanhoutte
P M
PM
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013552:Swine
D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D009569:Nitric Oxide; D000242:Cyclic AMP; D013482:Superoxide Dismutase; D006152:Cyclic GMP; D001920:Bradykinin