The kallikrein-kinin pathways in hypertension and diabetes.

Jagdish N Sharma, Parvathy Narayanan
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Abstract

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.

高血压和糖尿病的钾likrein-激肽通路。
心血管疾病是全世界最常见的死亡原因。高血压和糖尿病是导致心脏肥厚、缺血性心脏病和心力衰竭的两大危险因素。在科威特,高血压和糖尿病的发病率很高。先前的研究表明高血压和糖尿病中bk生成成分的活性改变。缓激肽是一种具有药理活性的多肽,可促进心血管和肾脏功能,如血管舒张、利钠、利尿和一氧化氮(NO)的释放。此外,B2激肽受体存在于心脏内皮细胞中,可能促进NO的生物合成和释放。已经证明尿(肾)钾激肽水平的降低可能与人类高血压和自发性高血压和糖尿病大鼠的发展有关。BK可能通过NO和环GMP的释放来产生其药理作用。此外,BK在心肌缺血中具有心脏保护作用,可以防止左心室肥厚。此外,携带组织激肽肽基因和过表达组织激肽肽的转基因小鼠血压降低。一氧化氮合酶和肾组织钾化肽均参与血压调节。kallikrein基因传递的能力和使用激肽B2受体激动剂产生广泛的有益作用,使其成为治疗高血压、心血管和肾脏疾病的有力候选者。激活激肽受体的策略可能适用于心血管疾病的治疗。糖尿病患者血浆钾激肽前升高可能是发生高血压和肾损害的一个指标。血浆和尿液中组织钾激肽的高浓度也可能导致血液中葡萄糖水平升高。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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