Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, Davis, CA 95616, USA.
J Physiol. 2010 Jan 15;588(Pt 2):325-39. doi: 10.1113/jphysiol.2009.180463. Epub 2009 Nov 30.
Atrial natriuretic peptide (ANP) via its guanylyl cyclase-A (GC-A) receptor participates in regulation of arterial blood pressure and vascular volume. Previous studies demonstrated that concerted renal diuretic/natriuretic and endothelial permeability effects of ANP cooperate in intravascular volume regulation. We show that the microvascular endothelial contribution to the hypovolaemic action of ANP can be measured by the magnitude of the ANP-induced increase in blood-to-tissue albumin transport, measured as plasma albumin clearance corrected for intravascular volume change, relative to the corresponding increase in ANP-induced renal water excretion. We used a two-tracer method with isotopically labelled albumin to measure clearances in skin and skeletal muscle of: (i) C57BL6 mice; (ii) mice with endothelium-restricted deletion of GC-A (floxed GC-A x tie2-Cre: endothelial cell (EC) GC-A knockout (KO)); and (iii) control littermates (floxed GC-A mice with normal GC-A expression levels). Comparison of albumin clearances in hypervolaemic EC GC-A KO mice with normovolaemic littermates demonstrated that skeletal muscle albumin clearance with ANP treatment accounts for at most 30% of whole body clearance required for ANP to regulate plasma volume. Skin microcirculation responded to ANP similarly. Measurements of permeability to a high molecular mass contrast agent (35 kD Gadomer) by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enabled repeated measures in individual animals and confirmed small increases in muscle and skin microvascular permeability after ANP. These quantitative methods will enable further evaluation of the contribution of ANP-dependent microvascular beds (such as gastro-intestinal tract) to plasma volume regulation.
心钠肽（ANP）通过其鸟苷酸环化酶-A（GC-A）受体参与调节动脉血压和血管容量。先前的研究表明，ANP 的协同肾脏利尿/利钠和内皮通透性作用共同参与血管内容量调节。我们表明，通过 ANP 诱导的血液向组织白蛋白转运增加的幅度来测量微血管内皮对 ANP 低血容量作用的贡献，该幅度通过血管内体积变化校正的血浆白蛋白清除率来测量，相对于 ANP 诱导的肾水排泄的相应增加。我们使用同位素标记白蛋白的双示踪剂方法测量了以下物质的清除率：（i）C57BL6 小鼠；（ii）内皮细胞（EC）GC-A 缺失（floxed GC-A x tie2-Cre：内皮细胞 GC-A 敲除（KO））的小鼠；和（iii）对照同窝仔（GC-A 表达水平正常的 floxed GC-A 小鼠）。将 EC GC-A KO 小鼠的高血容量状态下的白蛋白清除率与正常血容量的同窝仔进行比较，结果表明，在 ANP 调节血浆容量时，骨骼肌白蛋白清除率最多占全身清除率的 30%。皮肤微循环对 ANP 的反应也相似。通过动态对比增强磁共振成像（DCE-MRI）测量高相对分子质量对比剂（35 kD Gadomer）的通透性，使个体动物能够进行重复测量，并确认 ANP 后肌肉和皮肤微血管通透性有微小增加。这些定量方法将使我们能够进一步评估 ANP 依赖性微血管床（如胃肠道）对血浆容量调节的贡献。
