Understanding vasoactive hormone pathways in diabetic complications

高血压损害组织。在临床实践中，血压是在大动脉中测量的，例如手臂中的肱动脉。然而，实际上是肾脏等器官内的压力导致了损害。特别是肾脏的筛选装置（称为肾小球）对压力的影响特别敏感。在糖尿病中，肾小球内的压力很高，因为它的流出阀（称为传出小动脉）被紧紧地收缩。因此，即使血压被认为是正常的，当在手臂上测量时，它仍然可能在肾脏内过高。研究已经表明，降低肾内压可能对糖尿病肾病的进展产生重大影响。然而，迄今为止，肾内压的这种降低是次最大的。计划中的研究将涉及使用新的化合物，这些化合物在减少激素的形成或作用方面具有更强大的作用，这些激素促进肾脏血管收缩，导致肾脏内压力升高。此外，这些非常新的药物中的一些可以打开或扩张这些肾血管，从而实现肾内压力的极好降低。拟议的研究旨在检查优先将肾脏内压力降低到这些理想水平的新策略。这些激素还具有其他作用，可能与糖尿病中的非肾脏损伤部位有关，包括血管和视网膜。

High blood pressure damages tissues. In clinical practice blood pressure is measured in large arteries, such as the brachial artery in the arm. However, it is the pressure within the organ such as the kidney that actually causes the damage. In particular, the sieving apparatus of the kidney (called the glomerulus), is especially sensitive to the effects of pressure. In diabetes, the pressure within the glomerulus is high because its outflow valve (called the efferent arteriole) is tightly constricted. Therefore even if blood pressure is thought to be normal when measured in the arm, it may still be excessively high within the kidney. Studies have already shown that lowering within-kidney pressure may have a major impact on the progression of kidney disease in diabetes. However, to date this reduction of within-kidney pressure has been sub-maximal. The planned studies will involve the use of new compounds which have more powerful effects in reducing the formation or action of hormones which promote constriction of vessels in the kidney leading to elevated pressure within the kidney. Furthermore, some of these very new agents can open up or dilate these kidney vessels thereby achieving excellent reductions in the pressure inside the kidney. The proposed studies aim to examine new strategies for preferentially lowering pressure within the kidney down to these ideal levels. These hormones also have other effects which could be relevant to non-kidney sites of injury in diabetes including blood vessels and the retina.