Yang S T, Faraci F M, Heistad D D
Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242.
Hypertension. 1993 Aug;22(2):150-5. doi: 10.1161/01.hyp.22.2.150.
Endothelium-dependent dilatation of cerebral arterioles is impaired during chronic hypertension. The goal of this study was to determine the effects of an angiotensin converting enzyme inhibitor, cilazapril, on endothelium-dependent dilatation in pial arterioles. Four-month-old Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) received cilazapril in their drinking water (500 mg/L) for 3 to 6 months. Treatment with cilazapril reduced mean arterial pressure in both WKY rats and SHRSP and had no significant effect on baseline diameter of pial arterioles measured with a cranial window. Responses to bradykinin and A23187, but not to nitroglycerin and adenosine, were impaired in SHRSP. Cilazapril did not affect responses to bradykinin (3 x 10(-7) M) and A23187 (10(-5) M) in WKY rats but significantly increased cerebral vasodilatation in response to bradykinin (52 +/- 4% vs 27 +/- 5%) and A23187 (19 +/- 3% vs 8 +/- 3%) in SHRSP. Cilazapril also tended to increase dilator responses to nitroglycerin and adenosine in SHRSP. In another group of SHRSP, treatment with cilazapril for 4 days produced a moderate reduction in blood pressure and increased cerebral vasodilatation in response to bradykinin, A23187, and adenosine. Topical application of the active form of cilazapril (cilazaprilat) for 40 minutes also increased cerebral vasodilatation in response to bradykinin, A23187, and nitroglycerin in SHRSP. The data indicate that an angiotensin converting enzyme inhibitor enhances cerebral vasodilatation in response to endothelium-dependent agonists in SHRSP and may also increase responses to endothelium-independent agonists.
慢性高血压期间，脑小动脉的内皮依赖性舒张功能受损。本研究的目的是确定血管紧张素转换酶抑制剂西拉普利对软脑膜小动脉内皮依赖性舒张的影响。4月龄的Wistar-Kyoto（WKY）大鼠和易中风自发性高血压大鼠（SHRSP）饮用含西拉普利（500 mg/L）的水3至6个月。西拉普利治疗可降低WKY大鼠和SHRSP的平均动脉压，对用颅窗测量的软脑膜小动脉的基线直径无显著影响。SHRSP对缓激肽和A23187的反应受损，但对硝酸甘油和腺苷的反应未受损。西拉普利对WKY大鼠对缓激肽（3×10⁻⁷ M）和A23187（10⁻⁵ M）的反应无影响，但在SHRSP中可显著增加对缓激肽（52±4%对27±5%）和A23187（19±3%对8±3%）的脑血管舒张。西拉普利也倾向于增加SHRSP对硝酸甘油和腺苷的舒张反应。在另一组SHRSP中，用西拉普利治疗4天可使血压适度降低，并增加对缓激肽、A23187和腺苷的脑血管舒张。局部应用活性形式的西拉普利（西拉普利拉）40分钟也可增加SHRSP对缓激肽、A23187和硝酸甘油的脑血管舒张。数据表明，血管紧张素转换酶抑制剂可增强SHRSP对内皮依赖性激动剂的脑血管舒张，也可能增加对内皮非依赖性激动剂的反应。
