Kinin formation inhibition

Bik decreases ischemia/reperfusion injury by inhibiting proteases that cause kinin release [4, 99]. Reversion to a normal blood pressure occurs in two ways through inhibition of kallikrein with protease inhibitors and by destruction of kinins by kinase. Bik decreases kinin formation through their effect on kallikrein. The duration of kinin formation and destruction ranges from 2 to 30 min [100, 101]. After 30 min, little kinin activity is detectable. As inflammation abates, so does neutrophil chemotaxis and endothelial adherence to the basement membrane. PAR also regulates vascular tone and participates in response to vascular injury. Bik inhibits PAR activation [79, 80],... 

Ungar, Damgaard and Weinstein have shown that certain well recognized anti-inflammatory drugs, salicylic acid, phenazone, amidopyrine, cinchophen and also jf)-aminophenol inhibit fibrinolysin (plasmin) in concentrations close to those which show anti-inflammatory activity in vivo. Salicylate may inhibit kinin formation by this indirect mechanism involving plasmin. The failure of some workers to observe any inhibition of kallikrein by salicylate in vitro does not conflict with this. 

Antagonism of Kinin Formation and Action We have seen above (page 62) that bradykinin may be the intermediate factor responsible for many of the manifestations of inflammation. It is natural to consider the possibility that anti-inflammatory drugs may inhibit either the formation or the action of bradykinin. 

Northover and Subramanian report that formation of kinin by serum and salivary kallikrein is inhibited by sodium salicylate, acetylsalicylic acid, phenylbutazone and certain other anti-inflammatory substances. The vasodepressor and vascular permeability activities of kallikrein are similarly inhibited. These findings are not, however, supported by investigations of other workers and further studies are needed to clarify the discrepancy. It is interesting to note that hexadimethrine bromide(polybrene), which is known to inhibit kinin formation in vitro, inhibits increased capillary permeability in the xylene treated skin of mice . 

Muscle cells release kallikrein during inflammation causing formation of active kinin peptides (bradykinin and kallidin) from kininogen [65, 66]. Kinins are peptide hormones that produce vasodilation, increase capillary permeability, and cause pain and infiltration of neutrophils. There is a direct correlation between the amount of kinin in plasma or tissues and the degree of inflammation. Vascular dilation causes increased blood flow to infection [67, 68], Bik inhibits formation of kinins and vascular dilation by kallikrein, thereby inhibiting smooth muscle contraction [69-71],... 

Aspirin or acetylsalicylic acid, an ester of acetic acid, is the oldest known NSAID and the prototype of the salicylate drugs (Collier 1971, Rogstad Yndestad 1981). In addition to inhibition of COX, salicylates inhibit the formation and release of kinins, stabilize lysosomes and uncouple oxidative phosphorylation (Boothe 1995). In horses, the half-life of aspirin is very short. For example, in ponies, the elimination half-life of aspirin administered i.v. at a dose rate of 19 mg/kg was determined to be approximately 7min (Lees et al 1987a). 

All pathological conditions in man where kinins might play a role are associated with an increase in kinin release. The formation of unusual kinin or the inhibition of kininogenase activity has not thus far been proposed in any disease. 

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