Cardioprotective effects of vasopeptidase inhibition vs. angiotensin type 1-receptor blockade in spontaneously hypertensive rats on a high salt diet.
Cardioprotective effects of vasopeptidase inhibition vs. angiotensin type 1-receptor blockade in spontaneously hypertensive rats on a high salt diet.
复制标题
血管肽酶抑制与血管紧张素 1 型受体阻断对高盐饮食自发性高血压大鼠的心脏保护作用。
作者：
Tina Gröholm;P. Finckenberg;E. Palojoki;A. Saraste;T. Bäcklund;A. Eriksson;M. Laine;E. Mervaala;I. Tikkanen
我们的研究目的是比较血管肽酶抑制与血管紧张素1 （AT1）受体阻断利尿剂以及AT1受体阻断利尿剂联合利尿剂对高盐饮食原发性高血压大鼠模型的心脏保护作用。将73只自发性高血压大鼠（SHR）分为6组，给予低盐对照（NaCl 0.5%）饮食和药物治疗，疗程8周；2)高盐对照（NaCl 6%）；3)奥马帕特拉（40 mg/kg/d）高盐饮食；4)高盐饮食的氯沙坦（30 mg/kg/d）；5)氢氯噻嗪（HCTZ, 10 mg/kg/d）；6)氯沙坦+HCTZ （30+10 mg/kg/d）的高盐饮食。用尾袖容积描记仪测量血压。测定心肌损伤组织学评分、心肌胶原体积分数（CVF）、结缔组织生长因子（CTGF）表达及心肌细胞凋亡。作为一种降压药，omapatrilat比氯沙坦或HCTZ单药更有效，与氯沙坦+HCTZ联合治疗同样有效。心肌损伤评分显示，奥马帕特里拉和氯沙坦对心肌形态的保护作用优于盐酸戊二醇或联合用药。奥马帕特拉比其他疗法更能降低CVF，而氯沙坦在降低CTGF表达方面最有效。除HCTZ外，所有药物治疗均可减少心肌细胞凋亡。我们的研究结果提供了血管肽酶抑制和at1受体阻断在其降血压作用之外还具有心脏保护作用的证据。心脏保护与预防心肌细胞凋亡和抑制细胞外基质形成有关。
The aim of our study was to compare the cardioprotective effects of vasopeptidase inhibition with those of angiotensin type 1 (AT1)-receptor blockade, a diuretic and the combination of AT1-receptor blockade and a diuretic in an experimental rat model of essential hypertension on a high salt diet. Spontaneously hypertensive rats (SHR) (n =73) were divided into 6 groups to receive the following diet and drug regimens for 8 weeks: 1) low salt controls (NaCl 0.5%); 2) high salt controls (NaCl 6%); 3) omapatrilat (40 mg/kg/d) on a high salt diet; 4) losartan (30 mg/kg/d) on a high salt diet; 5) hydrochlorothiazide (HCTZ; 10 mg/kg/d) on a high salt diet; and 6) losartan+HCTZ (30+10 mg/kg/d) on a high salt diet. Blood pressure was measured by tail-cuff plethysmography. The histological score of myocardial damage, myocardial collagen volume fraction (CVF), connective tissue growth factor (CTGF) expression and cardiomyocyte apoptosis were determined. As an antihypertensive, omapatrilat showed greater efficacy than monotherapy with losartan or HCTZ, and was equally effective as the combination of losartan+HCTZ. Assessed by myocardial damage score, omapatrilat and losartan protected cardiac morphology better than HCTZ or the drug combination. Omapatrilat decreased CVF to a greater extent than the other therapies, whereas losartan was most effective in decreasing CTGF expression. All drug treatments, except HCTZ, decreased cardiomyocyte apoptosis. Our findings provide evidence that both vasopeptidase inhibition and AT1-receptor blockade exert cardioprotective properties beyond their blood pressure-lowering effects. Cardioprotection was associated with prevention of cardiomyocyte apoptosis and inhibition of extracellular matrix formation.
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影响因子：
15.9
作者：
Liu, YH;Yang, XP;Carretero, OA
通讯作者：
Carretero, OA
在没有心力衰竭的情况下，肌细胞肥大是中年个体肥大心脏中心室重塑的原因。
影响因子：
10.8
作者：
Olivetti,G;Melissari,M;Balbi,T;Quaini,F;Cigola,E;Sonnenblick,EH;Anversa,P
通讯作者：
Anversa,P
DOI：
--
发表时间：
1999
期刊：
Journal of hypertension. Supplement : official journal of the International Society of Hypertension
影响因子：
--
作者：
BurnettJr,JC
通讯作者：
BurnettJr,JC
影响因子：
158.5
作者：
Olivetti, G;Abbi, R;Anversa, P
通讯作者：
Anversa, P