Arvola P, Ruskoaho H, Wuorela H, Pekki A, Vapaatalo H, Pörsti I
Department of Biomedical Sciences, University of Tampere, Finland.
Br J Pharmacol. 1993 Apr;108(4):980-90. doi: 10.1111/j.1476-5381.1993.tb13495.x.
1 The effects of long-term angiotensin-converting enzyme inhibition with quinapril on arterial function were studied in spontaneously hypertensive rats, Wistar-Kyoto rats serving as normotensive controls. 2 Adult hypertensive animals were treated with quinapril (10 mg kg-1 day-1) for 15 weeks, which reduced their blood pressure and the concentrations of atrial natriuretic peptide in plasma and ventricular tissue to a level comparable with that in normotensive rats. 3 Responses of mesenteric arterial rings in vitro were examined at the end of the study. Compared with normotensive and untreated hypertensive rats, responses to noradrenaline were attenuated in hypertensive animals on quinapril, both force of contraction and sensitivity being reduced. Quinapril also attenuated maximal contractions but not sensitivity to potassium chloride. Nifedipine less effectively inhibited vascular contractions in normotensive and quinapril-treated than in untreated hypertensive rats. 4 Arterial relaxation responses by endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitrite, isoprenaline) mechanisms were similar in normotensive and quinapril-treated rats and more pronounced than in untreated hypertensive rats. 5 Cell membrane permeability to ions was evaluated by means of potassium-free solution-induced contractions of endothelium-denuded denervated arterial rings. These responses were comparable in normotensive and quinapril-treated rats and less marked than in untreated hypertensive rats. 6 Intracellular free calcium concentrations in platelets and lymphocytes, measured by the fluorescent indicator quin-2, were similar in normotensive and quinapril-treated rats and lower than in untreated hypertensive rats. 7 In conclusion, quinapril treatment improved relaxation responses and attenuated contractions in arterial smooth muscle of hypertensive rats. These changes may be explained by diminished cytosolic free calcium concentration, reduced cell membrane permeability, and alterations in dihydropyridine-sensitive calcium channels following long-term angiotensin-converting enzyme inhibition.
1 在自发性高血压大鼠中研究了用喹那普利长期抑制血管紧张素转换酶对动脉功能的影响，以Wistar - Kyoto大鼠作为正常血压对照。2 成年高血压动物用喹那普利（10毫克/千克/天）治疗15周，这使其血压以及血浆和心室组织中心房利钠肽的浓度降低到与正常血压大鼠相当的水平。3 在研究结束时检测了肠系膜动脉环的体外反应。与正常血压和未治疗的高血压大鼠相比，用喹那普利治疗的高血压动物对去甲肾上腺素的反应减弱，收缩力和敏感性均降低。喹那普利还减弱了最大收缩，但对氯化钾的敏感性未降低。硝苯地平在正常血压和用喹那普利治疗的大鼠中抑制血管收缩的效果不如在未治疗的高血压大鼠中有效。4 正常血压和用喹那普利治疗的大鼠中，通过内皮依赖性（乙酰胆碱）和内皮非依赖性（亚硝酸钠、异丙肾上腺素）机制的动脉舒张反应相似，且比未治疗的高血压大鼠更明显。5 通过无钾溶液诱导的去内皮去神经动脉环收缩来评估细胞膜对离子的通透性。这些反应在正常血压和用喹那普利治疗的大鼠中相当，且比未治疗的高血压大鼠中不明显。6 用荧光指示剂喹-2测量的血小板和淋巴细胞内游离钙浓度在正常血压和用喹那普利治疗的大鼠中相似，且低于未治疗的高血压大鼠。7 总之，喹那普利治疗改善了高血压大鼠动脉平滑肌的舒张反应并减弱了收缩。这些变化可能是由于长期抑制血管紧张素转换酶后，胞质游离钙浓度降低、细胞膜通透性降低以及二氢吡啶敏感性钙通道改变所致。
