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 i...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publications
2014-12-01
|
| Series: | Journal of the Renin-Angiotensin-Aldosterone System |
| Online Access: | https://doi.org/10.1177/1470320312474854 |
| Summary: | 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. |
|---|---|
| ISSN: | 1470-3203 1752-8976 |