title: Different cross-talk sites between the renin-angiotensin and the kallikrein-kinin systems.
abstract: Targeting the renin-angiotensin system (RAS) constitutes a major advance in the treatment of cardiovascular diseases. Evidence indicates that angiotensin-converting enzyme inhibitors and angiotensin AT1 receptor blockers act on both the RAS and the kallikrein-kinin system (KKS). In addition to the interaction between the RAS and KKS at the level of angiotensin-converting enzyme catalyzing both angiotensin II generation and bradykinin degradation, the RAS and KKS also interact at other levels: 1) prolylcarboxypeptidase, an angiotensin II inactivating enzyme and a prekallikrein activator; 2) kallikrein, a kinin-generating and prorenin-activating enzyme; 3) angiotensin-(1-7) exerts kininlike effects and potentiates the effects of bradykinin; and 4) the angiotensin AT1 receptor forms heterodimers with the bradykinin B2 receptor. Moreover, angiotensin II enhances B1 and B2 receptor expression via transcriptional mechanisms. These cross-talks explain why both the RAS and KKS are up-regulated in some circumstances, whereas in other circumstances both systems change in the opposite manner, expressed as an activated RAS and a depressed KKS. As the cross-talks between the RAS and the KKS play an important role in response to different stimuli, taking these cross-talks between the two systems into account may help in the development of drugs targeting the two systems.
authors: Inserm U955, Maisons-Alfort, France, and Faculté de Médecine de Créteil, Université Paris-Est, France jin-bo.su@inserm.fr.
authors: Jin Bo
authors: JB
authors: Su
mesh_terms: D006801:Humans; D016234:Kallikrein-Kinin System; D020239:Receptor Cross-Talk; D011956:Receptors, Cell Surface / Q000378:metabolism; D012084:Renin-Angiotensin System; D014158:Transcription, Genetic
chemical_list: D011956:Receptors, Cell Surface
keywords: AT1/B2 heterodimers; Angiotensin AT1 receptor blocker; angiotensin-converting enzyme inhibitor; cardiovascular disease; the kallikrein–kinin system; the renin–angiotensin system; transcriptional regulation