Production of cyclic GMP via activation of B1 and B2 kinin receptors in cultured bovine aortic endothelial cells.

The purpose of this study was to define the type of kinin receptors in bovine aortic endothelial cells. As a biochemical response we used the cyclic GMP production which can be attributed to the activation of the soluble guanylyl cyclase of the endothelial cells via endothelium-derived relaxing factor. For the first time we demonstrated that in addition to bradykinin (BK) the B1 kinin receptor agonist desArg9BK increased markedly the content of cyclic GMP. Similar to BK the desArg9BK-stimulated cyclic GMP production was transient and concentration dependent. The effects of both kinin agonists were inhibited by NG-nitro-L-arginine. The known B1 kinin receptor antagonist desArg9[Leu8] BK and the newly discovered antagonist desArg9D-Arg[Hyp3,Thi5,D-Tic7,Oic8]BK only inhibited the desArg9BK-stimulated cyclic GMP production. The B2 kinin receptor antagonists D-Arg[Hyp3,Thi5,D-Tic7,Oic8]BK and D-Arg[Hyp2,Thi5,8,D-Phe7]BK inhibited the production of cyclic GMP upon stimulation with BK and surprisingly also with desArg9BK. These findings indicate that bovine aortic endothelial cells possess B1 and B2 type kinin receptors which are associated with the production and/or release of endothelium-derived relaxing factor. Furthermore, it was shown for the first time that the B1 kinin receptor in bovine aortic endothelial cells seems to be quite different from that which exists in isolated tissue preparations. The functional importance of these B1 type receptors with regard to regulation of blood pressure and blood flow remains to be determined.