Cardiorenal association

肾功能与心血管疾病的发病率和病死率密切相关。抑制肾素-血管紧张素系统(RAS)和/或醛固酮可改善心力衰竭患者的预后。提示为了实现心肾保护，必须使用大剂量的RAS抑制剂。然而，由于血清肌酐或钾的升高，许多患者经常没有使用RAS阻滞剂或足够大的剂量。这项研究旨在阐明肾脏和心脏之间的联系机制。研究了防止RAS阻断引起的肾功能下降的方法。醛固酮的非基因组作用：我们研究了醛固酮在兔离体微灌流的传入或传出小动脉上的快速非基因组作用。在5分钟内，醛固酮可引起双侧小动脉血管收缩，其中传出小动脉的收缩作用更强。这种收缩不能被盐皮质激素受体阻滞剂阻断，但能被…阻断更多的磷脂酶C抑制剂。此外，去除内皮加强了收缩。我们的研究表明，醛固酮通过非基因组机制引起肾小球小动脉收缩。腺苷A1受体阻滞剂(AAB)对Dahl盐敏感大鼠(SSR)的影响：腺苷在肾内血流动力学中具有独特作用。我们研究了AAB或速尿(Fur)单独或联合依那普利(ENA)对SSR大鼠血压、肾功能和组织学的影响。免疫组织化学检测肾小球系膜细胞和肾小球上皮细胞的表型变化。ENA+FK组、ENA+Fur组和ENA+FK+Fur组大鼠尿蛋白排泄量和血肌酐水平均低于赋形剂组，存活率分别为27、71。分别为80%和88%。表型变化，特别是上皮细胞的表型变化，在最后一组中最小。我们认为，在SSR中，FK、ENA和Fur联合使用可抑制巨噬细胞的浸润，抑制系膜细胞和上皮细胞的表型变化，从而保护肾脏，提高存活率。较少

Close relation exists between the kidney function and cardiovascular morbidity/mortality. Inhibition of the renin-angiotensin system (RAS) and/or aldosterone improve outcome of patients with heart failure. It is suggested that in order to achieve cardiorenal protection, high doses of RAS inhibitors must be used. However, because of elevation of serum creatinine or potassium, many patients are often not treated with RAS blockers or high enough doses. This study aimed to clarify mechanisms that relate the kidney and heart. The means to prevent decline in renal function associated with RAS blockade were investigated.Non-genomic action of aldosterone : We studied a rapid non-genomic action of aldosterone in isolated microperfused rabbit afferent or efferent arterioles. Aldosterone induced vasoconstriction in both arterioles within 5 minutes, and the constriction was stronger in efferent arterioles. The constriction was not blocked with a mineralocorticoid receptor blocker but blocked with … More phospholipase C inhibitors. In addition, removal of the endothelium enhanced the constriction. Our studies suggest that aldosterone causes constriction of glomerular arterioles via nongenomic mechanisms.Effect of adenosine A1 receptor blocker (AAB) in Dahl salt sensitive rats (SSR) : Adenosine has unique actions in intrarenal hemodynamics. We studied the effect of AAB or furosemide (Fur) alone or in combination on top of enalapril (ENA) on blood pressure, renal function and histology in SSR. Phenotypic changes of mesangial and epithelial cells were also assessed with immunohistochemistry. Compared with vehicle group, urinary protein excretion and serum creatinine levels were lower in the ENA+FK, ENA+Fur and ENA+FK+Fur groups, and survival rate was 27, 71. 80 and 88%, respectively. Phenotypic changes, particularly those in epithelial cells, were least in the last group. We conclude that in SSR combination of FK, ENA and Fur inhibits macrophage infiltration, phenotypic changes in mesangial and epithelial cells, and thereby protects the kidney and improve survival rate. Less