Bradykinin deficiency

Cl inhibitor deficiency causes angioedema as a result of excessive bradykinin production. Thus the pathways and control mechanisms for bradykinin formation and... 

Han E, MacFarlane R, Mulhgan A, Scafidi J, Davis AR Increased vascular permeabihty in Cl inhibitor-deficient mice mediated by the bradykinin type 2 receptor. J Clin Invest 2002 8 1057-1063. 

A deficiency in the local synthesis of vasodilating substances in the vascular endothelium, such as prostacyclin, bradykinin, and nitric oxide, or an increase in production of vasoconstricting substances such as angiotensin II and endothelin I ... 

Trendelenburg AU, Meyer A, Klebroff W, Guimaraes S, Starke K (2003) Crosstalk between presynaptic angiotensin receptors, bradykinin receptors and a2-autoreceptors in sympathetic neurons a study in a2-adrenoceptor-deficient mice. Br J Pharmacol 138 1389-1402 Uchida H, Takeuchi H, Suzuki T, Nomura K, Watanabe K, Kashima H (2005) Combined treatment with sulpiride and paroxetine for accelerated response in patients with major depressive disorder. J Clin Psychopharmacol 25 545-51... 

Non-IgE-mediated anaphylactic reactions to polyacrylonitrile membranes have been reported (2,3). The effects are enhacing in those using ACE inhibitors (4,5), perhaps because of an effect of bradykinin (6), which is released by the membranes (2,8,9) and whose metabolism is inhibited by ACE inhibitors. The effects also occur to a lesser extent in those taking angiotensin receptor antagonists (7) and in those with Cl esterase inhibitor deficiency (10). Treating the membranes with polyethyleneimine prevents bradykinin release (11). 

Vascular endothelium and smooth muscle play important roles in regulating blood vessel tone and BP. These regulating functions are mediated through vasoactive substances that are synthesized by endothelial cells. It has been postulated that a deficiency in the local synthesis of vasodilating substances (e.g., prostacyclin and bradykinin) or excess vasoconstricting substances (e.g., angiotensin II and endothelin I) contribute to essential hypertension, atherosclerosis, and other diseases. 

Another possible function of C2 is in relation to the liberation of a kinin mediator (C-kinin) in the serum of patients with HANE (Donaldson et aL, 1969, 1970). It was found that HANE results from a severe deficiency of the Cl-INH protein or from structurally abnormal and functionally inactive Cl-INH (Donaldson et aL, 1963 Harpel et al, 1975). Thus activated Cl is increased in the serum of these patients, and on incubation a dialyzable and heat-stable mediator is released which increases vascular permeability and contracts smooth muscle without causing tachyphylaxis. The activity was inactivated by carboxypeptidase B and, unlike bradykinin, by trypsin, suggesting that the active principle is a polypeptide distinct from bradykinin, C3a and C5a anaphylatoxins (Donaldson et al, 1969). The liberation of this activity required Ci, C4, and C2 and was inhibited by added Cl-INH or antiserum to C4 or C2 but not by anti-C3 (Donaldson et al, 1969, 1970). In addition, the active principle was detected in the incubation mixture of refined ( s, C4, and C2 (Klemperer et al, 1969). Intradermal injection of active Cls increased vascular permeability in normal but not in C2-deficient patients (Klem-... 

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