The kallikrein-kinin pathways in hypertension and diabetes.

Cardiovascular diseases are the most common causes of mortality worldwide. Hypertension and diabetes are the two major risk factors in the development of cardiac hypertrophy, ischemic heart disease, and cardiac failure. In Kuwait, high rate of prevalence of hypertension and diabetes has been documented. Previous studies have indicated altered activities of the BK-generating components in hypertension and diabetes. Bradykinin is pharmacologically active polypeptide that can promote both cardiovascular and renal function, for example, vasodilation, natriuresis, diuresis, and release of nitric oxide (NO). In addition, B2 kinin receptors are present in the cardiac endothelial cells which may enhance the biosynthesis and release of NO. It has been demonstrated that reduced urinary (renal) kallikrein levels may be associated with the development of high blood pressure in humans and spontaneously hypertensive and diabetic rats. The BK may produce its pharmacological effects via NO and cyclic GMP release. Furthermore, it is established that the BK has cardioprotective actions in myocardial ischemia and can prevent left ventricular hypertrophy. Also, transgenic mice carrying tissue kallikrein gene and overexpressing tissue kallikrein had reduced blood pressure. NO synthase and renal tissue kallikrein are both involved in blood pressure regulation. The ability of kallikrein gene delivery and the use of kinin B2 receptor agonists to produce a wide spectrum of beneficial effects make it a powerful candidate in treating hypertension, cardiovascular, and renal diseases. Strategies that activate kinin receptors might be applicable to the treatment of cardiovascular disease. Increased plasma prekallikrein levels in diabetic patients may serve as an indicator of developing hypertension and renal damage. Also high plasma and urine concentrations of tissue kallikrein may cause higher glucose levels in the blood.