Kallikrein(K1)-kinin-kininase (ACE) and end-organ damage in ischemia and diabetes: therapeutic implications.
Genetic and pharmacological studies, clinical and experimental, focused on kallikrein-K1, kinin receptors and ACE/kininase II suggest that kinin release in the settings of ischemia or diabetes reduces organ damage, especially in the heart and kidney. Kinin bioavailability may be a limiting factor for efficacy of current kinin-potentiating drugs, like ACE inhibitors. Primary activation of kinin receptors by prototypic pharmacological agonists, peptidase-resistant, selective B1 or B2, displays therapeutic efficacy in experimental cardiac and peripheral ischemic and diabetic diseases. B1R agonism was especially efficient in diabetic animals and had no unwanted effects. Clinical development of kinin receptor agonists may be warranted.
Dorinne
D
Desposito
Ludovic
L
Waeckel
Louis
L
Potier
Christine
C
Richer
Ronan
R
Roussel
Nadine
N
Bouby
Francois
F
Alhenc-Gelas
D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism* / Q000628:therapy*; D006801:Humans; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000628:therapy*; D016234:Kallikrein-Kinin System / Q000187:drug effects