Different cross-talk sites between the renin-angiotensin and the kallikrein-kinin systems

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.

AT1/B2 heterodimers; Angiotensin AT1 receptor blocker; angiotensin-converting enzyme inhibitor; cardiovascular disease; the kallikrein–kinin system; the renin–angiotensin system; transcriptional regulation.