Cardiovascular diseases are the most common cause of death worldwide. In Kuwait, death related to cardio vascular diseases may account for about 40%. Thus, it will be the greatest health care burden of the twenty-first century. Hypertension and diabetes are the two major risk factors in the development of cardiac hypertrophy, ischemic heart disease, cardiac failure, cardiac arrhythmias and myocardial infarction. The kallikrein-kinin components (plasma and urinary kininogens, kallikreins, kininases and kinins) are able to regulate BP and blood glucose levels via promoting; vasodilator, natriuretic effects and glucose metabolism. These components are located in the cardiac tissue, kidney and vascular smooth muscle. The kinin system is found to be abnormally depressed in various experimental animal models of hypertension and diabetes which might be responsible for inducing cardiac complications. It has been pointed out that the development of a compound having renal kallikrein-like activity may serve the purpose of excreting excessive sodium from the kidney in the treatment of hypertension. Also it has been demonstrated that transgenic mice over-expressing renal tissue kallikrein were hypotensive and that administration of aprotinin, a tissue kallikrein inhibitor, restored the BP of the transgenic mice. These findings highlight a role of tissue kallikrein in the regulation of BP. It has been proposed that tissue kallikrein gene delivery into various hypertensive models exhibits protection, such as reduction in high BP, attenuation of cardiac hypertrophy, inhibition of renal damage and stenosis. This may indicate the prospect of this kallikrein gene therapy for cardiovascular pathology. Several reports indicate that urinary kallikrein excretion is decreased in essential hypertension in humans and in models of experimental hypertension. Thus, reduced urinary kallikrein may reflect a deficiency in the endogenous kallikrein/kinin vasodilatory system that contributes to the pathogenesis of hypertension. Previous studies conducted in white and black population in the USA demonstrated that urinary kallikrein excretion is diminished in family members at risk for hereditary (essential) hypertension and that urinary kallikrein is one of the major genetic markers associated with family history of hypertension. Also evidence for genetic linkage between the kallikrein locus and blood pressure has been reported in the rat. Previous studies have suggested that diminished urinary kallikrein excretion is associated with salt sensitivity of blood pressure. Kallikrein excretion is also diminished in African-Americans and deficiency of the kallikrein-kinin renal vasodilatory system may explain many of the unique features of essential hypertension and heart diseases in some black subjects.
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