Bennett M A, Hillier C, Thurston H
Department of Medicine and Therapeutics, Leicester Royal Infirmary, UK.
J Hypertens. 1996 Mar;14(3):389-97. doi: 10.1097/00004872-199603000-00017.
To examine the effects of different types of antihypertensive treatment on endothelium-dependent relaxation in resistance arteries from spontaneously hypertensive rats (SHRs).
Three-week-old SHRs were treated with the angiotensin converting enzyme (ACE) inhibitor perindopril (1 mg/kg/day) or quinapril (3 mg/kg/day) or the vasodilator hydralazine (50 mg/kg/day) or the calcium antagonist amlodipine (10 mg/kg/day). Control SHRs and Wistar-Kyoto (WKY) rats were treated with water. After 21 weeks rats were culled and mesenteric resistance arteries were mounted in a myograph. Relaxation responses to the endothelium-dependent vasodilators acetylcholine (ACh) and bradykinin were recorded before and after incubation with the nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NOARG), as was the relaxation response to the nitric oxide donor sodium nitroprusside (SNP).
All drugs prevented the rise in blood pressure found in the untreated SHRs. ACh-induced relaxation was significantly impaired in the untreated SHRs compared with the WKY rats. Treatment with either ACE inhibitor prevented the development of this impaired response. ACE inhibitor treatment significantly increased the relaxation response to bradykinin. Despite lowering blood pressure, hydralazine or amlodipine had no effect on ACh- or bradykinin-induced relaxation. Responses to SNP were not different between untreated SHRs and WKY rats and were not affected by drug treatment.
Specific properties of certain antihypertensive drugs may play an important role in restoring endothelium-dependent relaxation in the small arteries that regulate peripheral resistance in the SHR.
研究不同类型的抗高血压治疗对自发性高血压大鼠（SHR）阻力动脉内皮依赖性舒张功能的影响。
3周龄的SHR分别接受血管紧张素转换酶（ACE）抑制剂培哚普利（1 mg/kg/天）或喹那普利（3 mg/kg/天）、血管扩张剂肼屈嗪（50 mg/kg/天）或钙拮抗剂氨氯地平（10 mg/kg/天）治疗。对照SHR和Wistar-Kyoto（WKY）大鼠给予水。21周后处死大鼠，将肠系膜阻力动脉安装在肌动描记器上。在与一氧化氮合酶抑制剂NG-硝基-L-精氨酸（L-NOARG）孵育前后，记录对内皮依赖性血管扩张剂乙酰胆碱（ACh）和缓激肽的舒张反应，以及对一氧化氮供体硝普钠（SNP）的舒张反应。
所有药物均能防止未治疗的SHR血压升高。与WKY大鼠相比，未治疗的SHR中ACh诱导的舒张功能明显受损。使用任何一种ACE抑制剂治疗均可防止这种受损反应的发生。ACE抑制剂治疗显著增加了对缓激肽的舒张反应。尽管肼屈嗪或氨氯地平降低了血压，但对ACh或缓激肽诱导的舒张功能无影响。未治疗的SHR和WKY大鼠对SNP的反应无差异，且不受药物治疗影响。
某些抗高血压药物的特定特性可能在恢复调节SHR外周阻力的小动脉内皮依赖性舒张功能中起重要作用。
