Loutzenhiser R, Bidani A K, Wang X
Smooth Muscle Research Group, Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Acta Physiol Scand. 2004 Aug;181(4):407-13. doi: 10.1111/j.1365-201X.2004.01312.x.
The transmission of elevated blood pressure to the glomerulus and pressure-induced glomerular injury play central roles in the pathogenesis of kidney disease and its progression to end-stage renal failure. The renal afferent arteriole sets the pre-glomerular resistance and pressure-induced or 'myogenic' afferent arteriolar vasoconstriction is a primary mechanism protecting the glomerulus from the damaging effects of hypertension. The systolic pressure, being the highest level of pressure attained and most frequent pressure oscillation impacting on the renal vasculature, potentially represents the most damaging component of the blood pressure. Indeed, recent studies indicate that elevations in systolic blood pressure are more closely linked to kidney disease than are elevations in diastolic pressure. However, the current view, derived from dynamic studies of autoregulation, is that the renal vasculature responds passively to pressure signals presented at rates exceeding the myogenic operating frequency (0.2-0.3 Hz in the rat). Thus existing concepts do not explain the mechanisms that normally protect the kidney from elevations in the systolic pressure which are presented at the heart rate (6 Hz in the rat). A recent study from our laboratory addressed this issue. Using a modelling approach and direct measurements of myogenic responses, we found that the afferent arteriole is able to sense and appropriately adjust tone in response to changes in systolic pressure, presented at the heart rate. Key kinetic attributes allowing this vessel to respond in this manner appear to be a very short delay in activation, an unusually rapid rate of vasoconstriction and a longer delay in vasodilation. The present review summarizes this work and presents recent findings addressing the determinants of the myogenic vasoconstriction in the afferent arteriole.
血压升高传递至肾小球以及压力诱导的肾小球损伤在肾脏疾病的发病机制及其进展至终末期肾衰竭过程中起着核心作用。肾入球小动脉决定了肾小球前阻力，压力诱导的或“肌源性”入球小动脉血管收缩是保护肾小球免受高血压损害作用的主要机制。收缩压作为达到的最高压力水平以及对肾血管系统影响最频繁的压力波动，可能代表了血压中最具损害性的成分。事实上，最近的研究表明，收缩压升高比舒张压升高与肾脏疾病的联系更为紧密。然而，目前基于自动调节动态研究得出的观点是，肾血管系统对以超过肌源性工作频率（大鼠为0.2 - 0.3赫兹）的速率呈现的压力信号做出被动反应。因此，现有概念无法解释正常情况下保护肾脏免受以心率（大鼠为6赫兹）呈现的收缩压升高影响的机制。我们实验室最近的一项研究解决了这个问题。通过建模方法和对肌源性反应的直接测量，我们发现入球小动脉能够感知并根据以心率呈现的收缩压变化适当地调节张力。使该血管能够以这种方式做出反应的关键动力学特性似乎是激活延迟非常短、血管收缩速率异常快以及血管舒张延迟更长。本综述总结了这项工作，并介绍了关于入球小动脉肌源性血管收缩决定因素的最新研究结果。
