The evidence presented here suggests strongly that the kallikreins-kininogens-kinins-kininase II system has most significant role in regulation of systemic BP. This system is involved in mediation and modulation of renin-angiotensin-aldosterone, PGS and vasopressin in the regulation of sodium water balance, renal hemodynamic and BP. Therefore, reduction in the kinin-formation due to high production of kininase II, and lower formation of tissue kallikrein might result in an increased release of vasoconstrictor angiotensin II on one side, and on the other side much reduced production of PGE, vasodilator. These changes might lead to deranged vascular smooth muscle structures and cell membrane functions, retention of sodium and water, increased plasma volume, and renovascular constriction. These physiological defects might result in the development of essential hypertension (Fig. 4). Although, it is possible now to treat hypertensive conditions with tissue kallikrein and kininase II inhibitors. These discoveries have opened up new vistas to research on the pharmacological applications of kallikreins-kininogens-kinins-kininases in human diseases.
Components of the kallikrein-kininogen-kinin are activated in response to noxious stimuli (chemical, physical or bacterial), which may lead to excessive release of kinins in the synovial joints that may produce inflammatory joint disease. The inflammatory changes observed in synovial tissue may be due to activation of B2 receptors. Kinins also stimulate the synthesis of other pro-inflammatory agents (PGs, LTs, histamine, EDRF, PGI2 and PAF) in the inflamed joint. B2 receptor antagonists may provide valuable agents as new analgesic drugs. Further, it is suggested that substances directed to reduce the activation of KKS may provide a pharmacological basis for the synthesis of novel anti-rheumatic or anti-inflammatory drugs.
In recent years, numerous agents have been recognized as inflammatory mediators. In this review, however, we discuss only those having direct relevance to human inflammatory diseases These mediators are clinically important due to their proinflammatory properties such as vasodilatation, increased vascular permeability, pain and chemotaxis. They may lead to the fifth cardinal sign, loss of function in inflammatory diseases. Agonists and non-specific antagonists are used as pharmacological tools to investigate the inflammatory role of PGs, LTs, PAF, IL-1, histamine, complement, SP, PMN-leukocytes, and kallikrein-kininogen-kinin systems. Unfortunately, no compound is known which concurrently abolishes all actions and interactions of inflammatory mediators. Therefore it would be highly useful to promote efforts in developing selective and competitive antagonists against proinflammatory actions of these chemical mediators. This may help to a better understanding of the pathogenesis of inflammatory reactions, and it may also be useful for the therapy of inflammatory diseases.
This study examined the effects of streptozotocin-induced diabetes on blood pressure and cardiac tissue kallikrein levels in WKYR and SHR. Streptozotocin-induced diabetes caused significant (p < 0.001) increase in SBP and DBP in WKYR and SHR as compared with their respective controls. We also observed that the active cardiac tissue kallikrein levels reduced greatly (p < 0.001) in diabetic WKYR and SHR than the normal rats. These findings suggest for the first time that the cardiac tissue kallikrein formation may have a greater role in the regulation of blood pressure and cardiac function.