Understanding vasoactive hormone pathways in diabetic complications

高血压会损害组织。在临床实践中，血压是在大动脉中测量的，如手臂的肱动脉。然而，真正造成损害的是肾脏等器官内部的压力。特别是肾脏的筛分器官（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，因为它的流出瓣膜（称为传出小动脉）被紧紧收缩。因此，即使在手臂测量血压时被认为是正常的，肾脏内的血压仍然可能过高。研究已经表明，降低肾内压可能对糖尿病肾病的进展有重大影响。然而，到目前为止，这种肾内压力的降低还不是最大的。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的作用，激素会促进肾脏血管收缩，导致肾脏内压力升高。此外，其中一些非常新的药物可以打开或扩张这些肾血管，从而达到极好的降低肾内压力的效果。提出的研究旨在研究优先降低肾内压力至理想水平的新策略。这些激素也有其他作用，可能与糖尿病中非肾脏部位的损伤有关，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.