Gabbai F B, De Nicola L, Peterson O W, Obagi S, Thomson S C, Tucker B J, Keiser J A, Wilson C B, Blantz R C
Division of Nephrology-Hypertension, University of California, San Diego School of Medicine, USA.
J Am Soc Nephrol. 1996 Dec;7(12):2590-9. doi: 10.1681/ASN.V7122590.
Concurrent renal disease appears to augment greatly the adverse effects of systemic hypertension on renal function and the development of glomerulosclerosis. This study examined the effects of systemic hypertension and treatment of hypertension in groups of normal non-nephritic rats and rats submitted to 16 wk of glomerulonephritis induced by the administration of anti-glomerular basement membrane antibody. Hypertension was produced by application of a clip to the right renal artery and blood pressure was treated with an angiotensin-converting enzyme (ACE) inhibitor, quinapril. Glomerulosclerosis of two types developed: a diffuse type that is characteristic of anti-glomerular basement membrane glomerulonephritis, and a focal segmental glomerulosclerosis that is characteristic of systemic hypertension. Glomerulonephritis significantly reduced the capacity of ACE inhibitors to decrease systolic blood pressure in awake animals. In addition, glomerulonephritis produced significant effects on plasma angiotensin II concentrations, whereby ACE inhibition no longer lowered plasma angiotensin II levels and in fact produced an increase. Glomerular capillary hydrostatic pressure and hydrostatic pressure gradient correlated with systolic blood pressure and with the incidence of focal glomerulosclerosis in non-nephritic rats. However, in glomerulonephritis, systolic blood pressure no longer correlated with glomerular capillary pressure, and glomerular capillary pressure no longer correlated with the development of glomerulosclerosis, although systolic blood pressure did correlate with the degree of focal segmental glomerulosclerosis. Concurrent glomerulonephritis strongly conditions the effects of superimposed hypertension by altering the relationship between systemic blood pressure and glomerular capillary hydrostatic pressure and by decreasing the response of hypertension to therapy.
并发肾病似乎会极大地增强系统性高血压对肾功能和肾小球硬化发展的不良影响。本研究检测了系统性高血压以及高血压治疗对正常非肾炎大鼠组和经抗肾小球基底膜抗体诱导发生16周肾小球肾炎的大鼠组的影响。通过夹闭右肾动脉产生高血压，并用血管紧张素转换酶（ACE）抑制剂喹那普利治疗血压。出现了两种类型的肾小球硬化：一种是弥漫型，为抗肾小球基底膜肾小球肾炎的特征；另一种是局灶节段性肾小球硬化，为系统性高血压的特征。肾小球肾炎显著降低了ACE抑制剂在清醒动物中降低收缩压的能力。此外，肾小球肾炎对血浆血管紧张素II浓度产生了显著影响，由此ACE抑制不再降低血浆血管紧张素II水平，实际上反而使其升高。肾小球毛细血管静水压和静水压梯度与非肾炎大鼠的收缩压及局灶性肾小球硬化的发生率相关。然而，在肾小球肾炎中，收缩压不再与肾小球毛细血管压力相关，肾小球毛细血管压力也不再与肾小球硬化的发展相关，尽管收缩压确实与局灶节段性肾小球硬化的程度相关。并发肾小球肾炎通过改变系统性血压与肾小球毛细血管静水压之间的关系以及降低高血压对治疗的反应，强烈影响叠加性高血压的作用。
