Nakagawa H, Daihara M, Tamakawa H, Nozue T, Kawahara K
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
J Cardiovasc Pharmacol. 1999 Jul;34(1):28-33. doi: 10.1097/00005344-199907000-00005.
This study was designed to investigate the effects of the angiotensin-converting enzyme (ACE) inhibitor quinapril and the angiotensin II-receptor antagonist losartan on insulin sensitivity in two types of genetic hypertensive rats with insulin resistance. Quinapril (3 mg/kg) and losartan (10 mg/kg) decreased the systolic blood pressure to almost the same extent in both spontaneously hypertensive rats (SHRs) and Dahl salt-sensitive (Dahl S) rats. Quinapril increased the glucose requirement for the euglycemic clamp test in both SHRs and Dahl S rats, whereas losartan increased it in SHRs but not in Dahl S rats. The severity of the metabolic abnormalities may be responsible for the failure of losartan to improve the insulin sensitivity in Dahl S rats because serum insulin, total cholesterol, triglyceride, and free fatty acids (FFAs) were higher in the Dahl S rats than in SHRs. A kinin antagonist, Hoe 140, inhibited the increase in the glucose requirement by quinapril without affecting the depressor effect of quinapril in SHRs. In conclusion, quinapril improved the insulin sensitivity more effectively than did losartan in the genetic hypertensive rats with insulin resistance and relatively severe metabolic abnormalities. Based on our findings, one of the mechanisms underlying the difference between quinapril and losartan may thus be endogenous kinins.
本研究旨在探讨血管紧张素转换酶（ACE）抑制剂喹那普利和血管紧张素II受体拮抗剂氯沙坦对两种伴有胰岛素抵抗的遗传性高血压大鼠胰岛素敏感性的影响。喹那普利（3毫克/千克）和氯沙坦（10毫克/千克）在自发性高血压大鼠（SHR）和Dahl盐敏感（Dahl S）大鼠中，使收缩压降低的程度几乎相同。喹那普利增加了SHR和Dahl S大鼠正常血糖钳夹试验的葡萄糖需求量，而氯沙坦增加了SHR的葡萄糖需求量，但未增加Dahl S大鼠的葡萄糖需求量。代谢异常的严重程度可能是氯沙坦未能改善Dahl S大鼠胰岛素敏感性的原因，因为Dahl S大鼠的血清胰岛素、总胆固醇、甘油三酯和游离脂肪酸（FFA）水平高于SHR。激肽拮抗剂Hoe 140抑制了喹那普利引起的葡萄糖需求量增加，而不影响喹那普利对SHR的降压作用。总之，在伴有胰岛素抵抗和相对严重代谢异常的遗传性高血压大鼠中，喹那普利比氯沙坦更有效地改善了胰岛素敏感性。基于我们的研究结果，喹那普利和氯沙坦之间差异的潜在机制之一可能是内源性激肽。
