DE Gracia Maria C, Osuna Antonio, O'Valle Francisco, Del Moral Raimundo G, Wangensteen Rosemary, Del Rio Cipriano Garcia, Vargas Felix
Experimental Unit, Nephrology Service, Hospital Virgen de las Nieves, Granada, Spain.
Department of Anatomical Pathology, Faculty of Medicine, Granada, Spain.
J Am Soc Nephrol. 2000 Nov;11(11):1995-2000. doi: 10.1681/ASN.V11111995.
Chronic inhibition of the renin angiotensin system prevents increased BP and renal injury in N(G)-nitro-L-arginine methyl ester (L-NAME) hypertension. However, a relationship between plasma renin activity and the protective effect of chronic angiotensin II (Ang II) blockade has not been established. With this background, this study was undertaken to evaluate how the chronic administration of deoxycortisone acetate (DOCA) modifies the effects of losartan on BP, renal injury, and other variables in L-NAME hypertensive rats. The following groups were used: Control, DOCA, L-NAME, L-NAME + losartan, L-NAME + DOCA, and L-NAME + DOCA + losartan. Tail systolic BP was measured twice a week. After 4-wk evolution, mean arterial pressure and metabolic, morphologic, and renal variables were measured. The final mean arterial pressure values were 116 +/- 6 mmHg for control, 107 +/- 2 mmHg for DOCA, 151 +/- 5 mmHg for L-NAME, 123 +/- 2 mmHg for L-NAME + losartan, 170 +/- 3 mmHg for L-NAME + DOCA, and 171 +/- 5.5 mmHg for L-NAME + DOCA + losartan. Losartan prevented microalbuminuria, hyaline arteriopathy, and glomerulosclerosis of L-NAME hypertension but was ineffective in L-NAME + DOCA-treated rats. Plasma protein was significantly reduced in the L-NAME + DOCA group when compared with control and L-NAME groups, whereas no significant differences were observed in the other groups. Plasma renin activity was suppressed in the DOCA (0.55 +/- 0.2) and L-NAME + DOCA (0.60 +/- 10.2) groups but unsuppressed in the L-NAME + DOCA + losartan group (5.8 +/- 1). The conclusion is that DOCA blocks the preventive effect of losartan on the increased BP and renal injury of L-NAME hypertension, which suggests that DOCA transforms L-NAME hypertension into an Ang II-independent model of hypertension. These data also suggest that losartan prevents L-NAME hypertension by blocking the activity of systemic Ang II.
肾素-血管紧张素系统的慢性抑制可预防N（G）-硝基-L-精氨酸甲酯（L-NAME）高血压中血压升高和肾损伤。然而，血浆肾素活性与慢性血管紧张素II（Ang II）阻断的保护作用之间的关系尚未确立。在此背景下，本研究旨在评估醋酸脱氧皮质酮（DOCA）的慢性给药如何改变氯沙坦对L-NAME高血压大鼠血压、肾损伤及其他变量的影响。使用了以下几组：对照组、DOCA组、L-NAME组、L-NAME + 氯沙坦组、L-NAME + DOCA组和L-NAME + DOCA + 氯沙坦组。每周测量两次尾动脉收缩压。4周后，测量平均动脉压以及代谢、形态学和肾脏变量。对照组的最终平均动脉压值为116±6 mmHg，DOCA组为107±2 mmHg，L-NAME组为151±5 mmHg，L-NAME + 氯沙坦组为123±2 mmHg，L-NAME + DOCA组为170±3 mmHg，L-NAME + DOCA + 氯沙坦组为171±5.5 mmHg。氯沙坦可预防L-NAME高血压的微量白蛋白尿、透明样动脉病和肾小球硬化，但对L-NAME + DOCA治疗的大鼠无效。与对照组和L-NAME组相比，L-NAME + DOCA组的血浆蛋白显著降低，而其他组未观察到显著差异。DOCA组（0.55±0.2）和L-NAME + DOCA组（0.60±10.2）的血浆肾素活性受到抑制，但L-NAME + DOCA + 氯沙坦组（5.8±1）未受抑制。结论是，DOCA阻断了氯沙坦对L-NAME高血压中血压升高和肾损伤的预防作用，这表明DOCA将L-NAME高血压转变为一种不依赖Ang II的高血压模型。这些数据还表明，氯沙坦通过阻断全身Ang II的活性来预防L-NAME高血压。
