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Review
. 2002 Apr;109(8):1007-9.
doi: 10.1172/JCI15490.

The plasma kallikrein-kinin system counterbalances the renin-angiotensin system

Alvin H Schmaier  1
Affiliations
Review

The plasma kallikrein-kinin system counterbalances the renin-angiotensin system

Alvin H Schmaier. J Clin Invest. 2002 Apr.
No abstract available

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Figures

Figure 1
Figure 1
Assembly and activation of the plasma KKS on endothelial cells. Plasma PK circulates in complex with HK. The HK•PK complex binds to a multiprotein receptor complex that consists of cytokeratin 1 (CK1), urokinase plasminogen activator receptor (uPAR) and gC1qR. The proteins of the HK•PK receptor complex co-localize on endothelial cell membranes. When HK•PK binds to endothelial cells, PK is rapidly converted to kallikrein (K) by the enzyme prolylcarboxypeptidase (PRCP), which is constitutively active on endothelial cell membranes. The resulting kallikrein autodigests its receptor, HK, to liberate bradykinin (BK), which can liberate tissue plasminogen activator (tPA), nitric oxide (NO), and prostacyclin (PGI2) from endothelial cells. Kallikrein also activates FXII, which binds to the same multiprotein receptor complex as HK in its absence. In this revised hypothesis for assembly and activation of the proteins of the plasma KKS, FXII is activated by kallikrein after PK activation. ScuPA, single chain urokinase plasminogen activator.
Figure 2
Figure 2
The interaction between the plasma KKS and RAS. Plasma kallikrein converts prorenin to renin, and renin has the ability to convert angiotensinogen to angiotensin I. Angiotensin-converting enzyme (ACE) converts inactive angiotensin I to the vasoconstrictor angiotensin II. Angiotensin II stimulates plasminogen activator inhibitor 1 (PAI1) release from endothelial cells. At the same time ACE degrades bradykinin into bradykinin(1–7) (not shown) or bradykinin(1–5), a peptide with thrombin inhibitory activity. PRCP is the enzyme that degrades angiotensin II or angiotensin I to the vasodilating peptide, angiotensin II(1–7). Angiotensin II(1–7) stimulates NO and PGI2 formation, which potentiates the effects of bradykinin. PRCP also has the ability to convert PK to kallikrein. Formed kallikrein digests kininogens to liberate bradykinin, leaving a kinin-free kininogen (HKa) that has anti-proliferative and anti-angiogenic properties. Thus, PRCP, the same enzyme that degrades the vasoconstrictor angiotensin II, leads to the increased formation of the vasodilators bradykinin and angiotensin II(1–7). Finally, the resulting bradykinin stimulates tPA, NO, and PGI2 formation, thus counterbalancing the prothrombotic effect of angiotensin II.
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Comment on

References

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