Kinins metabolism

Proud D, Baumgarten CR, Naclerio RM, Ward PE (1987) Kinin metabolism in human nasal secretions during experimentally induced allergic rhinitis. J Immunol 138 428-434. 

ACE not only activates angiotensin but is also involved in the metabolism of other peptides, e.g., it is a major kinin-degrading enzyme. Therefore, ACE inhibitors also increase kinin concentrations. Furthermore, it has recently been shown that these drugs potentiate kinin effects by modulating a direct interaction between the ACE protein and the kinin B2 receptor, which is independent from the enzymatic activity of ACE. Kinin potentiation may be involved in the beneficial action of ACE inhibition since kinins are known to exert cardio- and renoprotective actions. 

The pathway for the formation and metabolism of kinins is shown in Figure 17-4. Three kinins have been identified in mammals bradykinin, lysylbradykinin (also known as kallidin), and methionyllysylbradykinin. Each contains bradykinin in its structure. 

Kinins are metabolized rapidly (half-life < 15 seconds) by nonspecific exopeptidases or endopeptidases, commonly referred to as... 

The synthesis of kinins can be inhibited with the kallikrein inhibitor aprotinin. Actions of kinins mediated by prostaglandin generation can be blocked nonspecifically with inhibitors of prostaglandin synthesis such as aspirin. Conversely, the actions of kinins can be enhanced with ACE inhibitors, which block the degradation of the peptides. Indeed, as noted above, inhibition of bradykinin metabolism by ACE inhibitors contributes significantly to their antihypertensive action. 

In contrast to the adverse physiologies associated with bradykinin release, there is a growing body of literature that implicates bradykinin as a protective agent during periods of cardiac or renal stress [14-16]. In this regard there is substantial evidence that the cardioprotective effects afforded by ACE-inhibitor treatment are a result of metabolically preserving bradykinin and are therefore mediated by bradykinin B2 (and possibly 1) receptors [17-18]. These results point to a possible therapeutic role for a kinin receptor agonist. 

ANTI HYPERTENSIVES AND HEART FAILURE DRUGS NS AIDs 1 hypotensive effect, especially with indometacin. The effect is variable amongst different ACE inhibitors and NSAIDs, but is most notable between captopril and indometacin NSAIDs cause sodium and water retention and raise BP by inhibiting vasodilating renal prostaglandins. ACE inhibitors metabolize tissue kinins (e.g. bradykinin) and this may be the basis for indometacin attenuating hypotensive effect of captopril Monitor BP at least weekly until stable. Avoid co administering indometacin with captopril... 

The Endogenous Kallikrein-Kininogen-Kinin System SYNTHESIS AND METABOLISM OF KININS... 

Dual blockade of the RAS is based on a principle of obtaining more efficient blockade of the effects of angiotensin 11, by combining ACE-1 and ARB. ARB produces a complete blockade of the RAS and stimulates the vasodilating and nonproliferative actions of All via the AT-2 receptor. Furthermore, ACE-1, but not ARB, inhibit the metabolism of kinins, which increases the level of bradykinin, a potent vasodilator. 

Fletcher RA, Zalik S (1965) Effect of light of several spectral bands on the metabolism of radioactive lAA in bean seedlings. Plant Physiol 40 549-552 Fox JE, Weis JS (1965) Transport of the kinin, N -benzyladenine non-polar or polar Nature 206 678-679... 

The impact of biochemistry on all phases and aspects of the inflammatory process is most impressive. Studies embrace in vitro models, protein synthesis inhibition, protein binding, immiunosuppression, metabolism of collagen, specific mechanisms of action and the role of mediators, particularly kinins. 

As discussed earlier, CatA is strongly involved in urinary bradykinin metabolism in rat and humans. Therefore, elevated bradykinin levels after CatA inhibition should result in increased diuresis. Based on these considerations, the group of Majima investigated effects on urinary kinin levels, natriuresis, and diuresis after administration of the CatA inhibitor ebelactone B to rats [48,49]. Using a sophisticated experimental protocol with cannulated ureters in anesthetized animals. 

Now the kininogen-kinins system, when activated, strongly affects the blood pressure. Epinephrine for example could activate this metabolic system (Back 1906, Sicuteri et al. 1963, Periti et al. 1963). 

We hypothesized then that this kininogenolysis may be considered as one of the metabolic phenomena induced by epinephrine. Before our studies, Hilton and Lewis (1958) demonstrated in animals an increase in kinin while perfusing the salivary gland with adrenalia This problem then seemed to merit more extensive research to confirm the probable kininogenolytic effect of epinephrine and to try understand, with the help of beta-blocking agents, if this effect may be coupled really to beta-receptor stimulation. 

The second clinico-pharmacologieal aspect of adrenaline remains to be considered. This hormone, also in non vasoactive, but only "metabolic" doses evokes clinical pains as those of angina pectoris and migraine. The kinin release may be implicated in fact the injection of bradykinin or kallikrein is able to induce identical effects. 

In angina pectoris as in headache the attacks induced by emotional stress of by injection of vasoactive doses of adrenaline may be mediated partially by the kinin mechanism, however the increase of heart work and respectively the dilatation of head vessels remain the primary factors. On the other hand, when angina pectoris is induced by slow infusion of non vasoactive but only metabolic amounts of adrenaline the most reliable mechanism appears that of the kinins. In this case at least apparently, the heart and vascular motor beta-... 

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