Effects of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Type 1 Receptor Antagonist in Deoxycorticosterone Acetate–Salt Hypertensive Mice Lacking Ren-2 Gene
Effects of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Type 1 Receptor Antagonist in Deoxycorticosterone Acetate–Salt Hypertensive Mice Lacking Ren-2 Gene
复制标题
血管紧张素转换酶抑制剂和血管紧张素 1 型受体拮抗剂对缺乏 Ren-2 基因的脱氧皮质酮醋酸盐高血压小鼠的影响
作者：
Hongmei Peng;O. Carretero;M. Alfie;Julie A. Masura;N. Rhaleb
我们以前报道过，抑制血管紧张素转换酶（ACE）可以预防由脱氧皮质酮醋酸盐（DOCA盐）诱导的129/SvEvTac小鼠的高血压和左心室肥厚，该小鼠具有2个肾素基因（Ren-1和Ren-2）。在本研究中，我们通过单侧肾切除术和DOCA-盐诱导仅具有Ren-1基因的小鼠（C57 BL/6 J）的高血压，并研究ACE抑制剂（雷米普利，4 mg · kg-1 · d-1）和血管紧张素1型（AT 1）受体拮抗剂（L-158809，4 mg · kg-1 · d-1）对高血压、心脏肥大和肾损伤的影响。治疗4周后，DOCA-盐小鼠的收缩压（128±2 mm Hg）与对照组（109±2 mm Hg）相比显著升高（P <0.001），而血浆肾素浓度降低了97%（P <0.001）。DOCA盐还诱导左心室和肾肥大以及肾损伤，如蛋白尿所示。DOCA-盐组小鼠左心室和肾脏胶原含量显著高于对照组（P <0.001）。DOCA盐组大鼠尿白蛋白（P <0.05）、肾小管和肾皮质增殖细胞核抗原阳性细胞（P <0.001）明显增多。ACE抑制剂和AT 1拮抗剂均无任何降压作用，但可部分预防心肌肥厚，并完全抑制左心室胶原沉积。在肾脏中，ACE抑制剂和AT 1拮抗剂部分减少胶原的增加，但对肥大没有影响。它们还显著防止DOCA盐对尿白蛋白和肾脏中增殖细胞核酸抗原表达的影响。尽管缺乏抗高血压作用，但ACE抑制剂和AT 1拮抗剂均能预防心脏重塑和肾损害。我们的研究结果表明，ACE抑制剂和AT 1拮抗剂发挥有益的影响，心脏和肾脏DOCA盐高血压小鼠独立的血压的影响。
We previously reported that inhibition of angiotensin-converting enzyme (ACE) prevented the hypertension and left ventricular hypertrophy induced by deoxycorticosterone acetate–salt (DOCA-salt) in 129/SvEvTac mice, which have 2 renin genes (Ren-1 and Ren-2). In the present study, we induced hypertension by uninephrectomy and DOCA-salt in mice having only the Ren-1 gene (C57BL/6J) and investigated the effect of an ACE inhibitor (ramipril, 4 mg · kg−1 · d−1) and an angiotensin type 1 (AT1) receptor antagonist (L-158809, 4 mg · kg−1 · d−1) on the development of hypertension, cardiac hypertrophy, and renal injury. After 4 weeks of treatment, systolic blood pressure in DOCA-salt mice was significantly increased (128±2 mm Hg) compared with controls (109±2 mm Hg) (P <0.001), while plasma renin concentration was decreased by 97% (P <0.001). DOCA-salt also induced left ventricular and renal hypertrophy and renal damage as manifested by proteinuria. Collagen content in the left ventricle and kidney was significantly higher in DOCA-salt mice (P <0.001). Urinary albumin (P <0.05) and proliferating cell nucleic antigen–positive cells in the tubules and interstitium of the renal cortex (P <0.001) were significantly increased in the DOCA-salt group. Neither the ACE inhibitor nor the AT1 antagonist had any antihypertensive effect; however, they partially prevented cardiac hypertrophy and completely inhibited left ventricular collagen deposition. In the kidney, both the ACE inhibitor and AT1 antagonist partially reduced the increase in collagen but had no effect on hypertrophy. They also significantly prevented the effect of DOCA-salt on urinary albumin and proliferating cell nucleic antigen expression in the kidney. Despite the lack of an antihypertensive effect, both ACE inhibitor and AT1 antagonist prevented cardiac remodeling and renal damage. Our results indicate that ACE inhibitors and AT1 antagonists exert beneficial effects on the heart and kidney in DOCA-salt hypertensive mice independently of their effects on blood pressure.
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影响因子：
8.3
作者：
Gallagher, AM;Yu, H;Printz, MP
通讯作者：
Printz, MP
影响因子：
8.3
作者：
Liu, YH;Yang, XP;Carretero, OA
通讯作者：
Carretero, OA
影响因子：
158.5
作者：
BRENNER, BM;MEYER, TW;HOSTETTER, TH
通讯作者：
HOSTETTER, TH
影响因子：
8.3
作者：
S. Saitoh;A. Scicli;E. Peterson;O. Carretero
通讯作者：
S. Saitoh;A. Scicli;E. Peterson;O. Carretero
影响因子：
15.9
作者：
Liu, YH;Yang, XP;Carretero, OA
通讯作者：
Carretero, OA