Vacher E, Richer C, Giudicelli J F
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France.
J Hypertens. 1996 Nov;14(11):1341-8. doi: 10.1097/00004872-199611000-00013.
To investigate in young salt-loaded stroke-prone spontaneously hypertensive rats (SHR-SP) the effects of a long-term administration of the angiotensin II AT1 receptor antagonist losartan [1 mg/kg (L1) and 10 mg/kg (L10) per day, from 5 to 20 weeks of age] on the structural and functional characteristics of the middle cerebral artery.
Morphological measurements and isometric tension recordings (myograph, contractile responses to potassium chloride and serotonin, relaxant responses to bradykinin and sodium nitroprusside) were performed on isolated vessels from randomly selected control and losartan-treated SHR-SP and age-matched Wistar-Kyoto (WKY) rats killed at ages 6-7, 10-11 and 16-17 weeks.
Whereas all control SHR-SP had died within 18 weeks of being born, losartan at both doses afforded full protection against stroke and mortality. Losartan limited malignant hypertension development dose-dependently. Age-related increases in cerebral arterial wall thickness and wall:lumen ratio were not affected (L1) or limited slightly (L10) by losartan. In control SHR-SP, contractile responses of cerebral arteries to agonists decreased with ageing and stroke occurrence and were significantly smaller than those of age-matched WKY rat arteries. Losartan limited the cerebrovascular contractility impairment dose-dependently in SHR-SP but did not affect the WKY rat cerebral artery contractility. In addition, losartan limited the age-related alteration of the endothelium-dependent relaxation of cerebral arteries observed in control SHR-SP dose-dependently.
In SHR-SP, losartan prevented stroke and improved the cerebral artery's smooth muscle and endothelial cell functions, which are altered during ageing and impaired even more dramatically by stroke occurrence.
研究在年轻的盐负荷易中风自发性高血压大鼠（SHR-SP）中，长期给予血管紧张素II AT1受体拮抗剂氯沙坦[从5至20周龄，每天1 mg/kg（L1）和10 mg/kg（L10）]对大脑中动脉结构和功能特征的影响。
对随机选取的对照组和氯沙坦治疗的SHR-SP以及年龄匹配的Wistar-Kyoto（WKY）大鼠（在6-7周龄、10-11周龄和16-17周龄处死）的分离血管进行形态学测量和等长张力记录（肌动描记法，对氯化钾和5-羟色胺的收缩反应，对缓激肽和硝普钠的舒张反应）。
所有对照SHR-SP在出生后18周内死亡，而两种剂量的氯沙坦都能提供完全的中风和死亡保护。氯沙坦剂量依赖性地限制恶性高血压的发展。大脑动脉壁厚度和壁:腔比值随年龄的增加不受氯沙坦影响（L1）或略有受限（L10）。在对照SHR-SP中，大脑动脉对激动剂的收缩反应随年龄增长和中风发生而降低，且显著小于年龄匹配的WKY大鼠动脉。氯沙坦在SHR-SP中剂量依赖性地限制脑血管收缩功能损害，但不影响WKY大鼠大脑动脉收缩功能。此外，氯沙坦剂量依赖性地限制了对照SHR-SP中观察到的大脑动脉内皮依赖性舒张的年龄相关改变。
在SHR-SP中，氯沙坦预防了中风，并改善了大脑动脉的平滑肌和内皮细胞功能，这些功能在衰老过程中发生改变，且因中风发生而受损更显著。
