Dupuis François, Atkinson Jeffrey, Limiñana Patrick, Chillon Jean-Marc
Cardiovascular Research Group, INSERM U684, Faculté de Pharmacie, Université Henri Poincaré-Nancy I, Nancy, France.
J Hypertens. 2005 May;23(5):1061-6. doi: 10.1097/01.hjh.0000166848.95592.a5.
Antihypertensive treatment with angiotensin-converting enzyme inhibitors (ACEIs) reverses cerebral arteriolar remodeling, thus restoring dilatation and hence the lower limit of cerebral blood flow (CBF) autoregulation (LLCBF). The objective of this study was to determine whether angiotensin II receptor AT1 blockers (ARBs) produce the same effect.
We examined the effects of treatment with an ARB [telmisartan (TEL), 1.93 +/- 0.04 mg/kg per day] or an ACEI [ramipril (RAM), 1.00 +/- 0.02 mg/kg per day] on the cerebral circulation in spontaneously hypertensive rats (SHR).
Arteriolar pressure and diameter (cranial window) and CBF (laser Doppler) were measured during stepwise hypotensive hemorrhage, before and after deactivation (ethylenediamine tetraacetic acid), in untreated Wistar-Kyoto (WKY) rats and SHR untreated or treated for 3 months with TEL or RAM in the drinking water.
Treatment normalized arteriolar internal diameter (SHR, 38 +/- 3 microm; TEL, 52 +/- 2 microm; RAM, 50 +/- 2 microm; WKY, 58 +/- 4 microm), essentially by reversing eutrophic inward remodeling, and the LLCBF (SHR, 80 +/- 11 mmHg; TEL, 60 +/- 4 mmHg; RAM, 71 +/- 6 mmHg; WKY, 57 +/- 5 mmHg).
The fact that the ARB (TEL) is as effective as an ACEI (RAM) in reversing cerebral arteriolar remodeling suggests that the cerebrovascular AT1 receptor is an underlying mechanism that promotes hypertensive eutrophic inward remodeling.
使用血管紧张素转换酶抑制剂(ACEI)进行抗高血压治疗可逆转脑小动脉重塑,从而恢复血管舒张功能以及脑血流量(CBF)自动调节的下限(LLCBF)。本研究的目的是确定血管紧张素II受体AT1阻滞剂(ARB)是否具有相同的效果。
我们研究了使用ARB[替米沙坦(TEL),每天1.93±0.04mg/kg]或ACEI[雷米普利(RAM),每天1.00±0.02mg/kg]对自发性高血压大鼠(SHR)脑循环的影响。
在未治疗的Wistar-Kyoto(WKY)大鼠和未治疗或饮用含TEL或RAM的水3个月的SHR中,在逐步降压性出血期间、失活(乙二胺四乙酸)前后,测量小动脉压力和直径(颅窗)以及CBF(激光多普勒)。
治疗使小动脉内径恢复正常(SHR,38±3微米;TEL,52±2微米;RAM,50±2微米;WKY,58±4微米),主要是通过逆转肥厚性内向重塑以及LLCBF(SHR,80±11mmHg;TEL,60±4mmHg;RAM,71±6mmHg;WKY,57±5mmHg)来实现的。
ARB(TEL)在逆转脑小动脉重塑方面与ACEI(RAM)同样有效,这一事实表明脑血管AT1受体是促进高血压性肥厚性内向重塑的潜在机制。