Multiple interactions between the renin-angiotensin and the kallikrein-kinin systems: role of ACE inhibition and AT1 receptor blockade.
The investigation of therapeutic actions of angiotensin type 1 (AT1) receptor antagonists and ACE inhibitors (ACEI) demonstrated complex interactions between the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS) in several experimental and clinical studies. They are evidenced by the fact that (1) ACE efficiently catabolizes kinins; (2) angiotensin-derivatives such as ANG-(1-7) exert kininlike effects; and (3) kallikrein probably serves as a prorenin-activating enzyme. (4) Several authors have demonstrated experimentally that the protective effects of ACEI are at least partly mediated by a direct potentiation of kinin receptor response on BK stimulation. (5) Furthermore, studies on AT1 antagonists, which do not directly influence kinin degradation, and studies on angiotensin-receptor transgenic mice have revealed additional interactions between the RAS and the KKS. There is mounting evidence that an autocrine cascade including kinins, nitric oxide, prostaglandins, and cyclic GMP is involved in at least some of the angiotensin type 2 receptor effects. This review discusses multiple possibilities of cross-talks between the RAS and KKS in vascular and cardiac physiology and pathology after ACE inhibition and AT1 receptor blockade.
Tschöpe
Carsten
C
Department of Cardiology and Pneomology, University Hospital Benjamin Franklin, Free University of Berlin, Hindenburgdamm 30, D-12220 Berlin, Germany. ctschoepe@yahoo.com
Schultheiss
Heinz-Peter
HP
Walther
Thomas
T
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000096:biosynthesis; D006801:Humans; D016234:Kallikrein-Kinin System / Q000187:drug effects* / Q000502:physiology; D020239:Receptor Cross-Talk; D044140:Receptor, Angiotensin, Type 1; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin / Q000378:metabolism; D018002:Receptors, Bradykinin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin; D018002:Receptors, Bradykinin; D001920:Bradykinin