Dohi Y, Criscione L, Pfeiffer K, Lüscher T F
Department of Medicine, University Hospitals Basel, Switzerland.
J Cardiovasc Pharmacol. 1994 Sep;24(3):372-9. doi: 10.1097/00005344-199409000-00004.
Endothelial regulation of peripheral vascular resistance is impaired in hypertension. We studied the effects of different antihypertensive therapies on endothelial function in perfused mesenteric resistance arteries. Spontaneously hypertensive rats (SHR) aged 7 weeks were treated with either the nonpeptidic angiotensin II (AII) receptor antagonist CGP 48369, the angiotensin-converting enzyme (ACE) inhibitor benazepril HCl, or the calcium antagonist nifedipine (each 10 mg/kg/day orally, p.o.) for 8 weeks. All forms of therapy inhibited the increase in systolic blood pressure (SBP) to a comparable degree (18-23 mm Hg) and reduced but did not normalize medial hypertrophy in SHR. Changes in intraluminal vascular diameter to acetylcholine (ACh), norepinephrine (NE), and endothelin-1 (ET-1) were measured. Impaired endothelium-dependent relaxations to intraluminal ACh improved or normalized with all therapies, whereas the response to extraluminal ACh (which was unimpaired in SHR) remained unaffected. The endothelium-dependent inhibition of contractions to NE was lost in untreated SHR and improved or restored by antihypertensive therapy. In SHR, the sensitivity but not the maximal response of vascular smooth muscle (VSM) to ET-1 was paradoxically decreased. Antihypertensive therapy with CGP 48369, nifedipine, or benazepril HCl restored or increased the sensitivity to ET-1. Thus, chronic blockade of the renin-angiotensin system or voltage-operated calcium channels reduces BP and improves endothelial dysfunction in the resistance circulation of SHR. This may contribute to normalization of peripheral vascular resistance during antihypertensive treatment and improve local blood flow to vital organs.
高血压患者外周血管阻力的内皮调节功能受损。我们研究了不同抗高血压疗法对灌注肠系膜阻力动脉内皮功能的影响。对7周龄的自发性高血压大鼠（SHR）分别给予非肽类血管紧张素II（AII）受体拮抗剂CGP 48369、血管紧张素转换酶（ACE）抑制剂盐酸贝那普利或钙拮抗剂硝苯地平（均为口服，10 mg/kg/天），持续治疗8周。所有治疗方式均能将收缩压（SBP）升高抑制到相当程度（18 - 23 mmHg），并减轻了SHR的血管中层肥厚，但未使其恢复正常。测量了血管腔内直径对乙酰胆碱（ACh）、去甲肾上腺素（NE）和内皮素 - 1（ET - 1）的变化。所有治疗均使对腔内ACh的内皮依赖性舒张功能受损得到改善或恢复正常，而对腔外ACh的反应（SHR中未受损）则不受影响。在未治疗的SHR中，对NE收缩反应的内皮依赖性抑制作用丧失，而抗高血压治疗使其得到改善或恢复。在SHR中，血管平滑肌（VSM）对ET - 1的敏感性而非最大反应却反常地降低。用CGP 48369、硝苯地平或盐酸贝那普利进行抗高血压治疗可恢复或增加对ET - 1的敏感性。因此，肾素 - 血管紧张素系统或电压门控钙通道的长期阻断可降低血压并改善SHR阻力循环中的内皮功能障碍。这可能有助于抗高血压治疗期间外周血管阻力的正常化，并改善重要器官的局部血流。
