Millette Esther, Demeilliers Bénédicte, Wu Rong, Laplante Marc-André, El Midaoui Adil, Moreau Pierre, Lamontagne Daniel, de Champlain Jacques
Faculté de pharmacie, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Quebec, Canada, H3C 3J7.
J Hypertens. 2003 Jan;21(1):125-35. doi: 10.1097/00004872-200301000-00022.
To compare the cardiovascular protection provided by omapatrilat and lisinopril in an experimental model of hypertension.
Four-week deoxycorticosterone acetate (DOCA)-salt hypertensive (HT) and age-matched normotensive (NT) rats were treated either with omapatrilat (40 mg/kg per day) or lisinopril (20 mg/kg per day) for 2 weeks before sacrifice, and compared with untreated HT and NT rats sacrificed at ages corresponding to either before or after the drug regimens.
Systolic arterial pressure (SAP) of 2 and 4 week HT rats was increased in comparison to age-matched NT rats (P <0.05). Treatment with omapatrilat or lisinopril reduced SAP in HT (P <0.05) similarly by about 10%. Cardiac interstitial collagen, perivascular collagen and media/lumen ratio of coronary arterioles were increased in HT rats. Both treatments partially prevented the rise in perivascular collagen and completely corrected the increased media/lumen ratio in small arterioles from HT (P <0.05). In contrast to NT rats, only a weak coronary dilatation to bradykinin was observed in Langendorff hearts isolated from untreated-HT. This response was slightly improved by lisinopril and markedly improved by omapatrilat (P <0.05). The coronary dilatation to SNP which was reduced in 4-week HT (P <0.05), was partially improved by omapatrilat treatment but not by lisinopril. The enhanced superoxide anion production in aorta from HT rats was partially corrected with omapatrilat and lisinopril. Finally, omapatrilat, unlike lisinopril, markedly reduced mortality in a more severe form of DOCA-salt hypertension.
Omapatrilat and lisinopril regressed coronary remodelling and cardiac collagen deposition, and reduced vascular oxidative stress in DOCA-salt hypertensive rats. However, despite similar antihypertensive efficacy, omapatrilat was superior to lisinopril in improving the endothelial-dependent coronary dilatation, suggesting a better vascular protection in the DOCA-salt model of hypertension.
在高血压实验模型中比较奥美沙坦酯和赖诺普利提供的心血管保护作用。
四周龄醋酸脱氧皮质酮（DOCA）-盐诱导的高血压（HT）大鼠和年龄匹配的正常血压（NT）大鼠，在处死前用奥美沙坦酯（每天40mg/kg）或赖诺普利（每天20mg/kg）治疗2周，并与在药物治疗前或后的相应年龄处死的未治疗的HT和NT大鼠进行比较。
与年龄匹配的NT大鼠相比，2周龄和4周龄HT大鼠的收缩压（SAP）升高（P<0.05）。奥美沙坦酯或赖诺普利治疗使HT大鼠的SAP类似地降低约10%（P<0.05）。HT大鼠的心脏间质胶原、血管周围胶原以及冠状动脉小动脉的中膜/管腔比增加。两种治疗均部分阻止了血管周围胶原的增加，并完全纠正了HT大鼠小动脉中膜/管腔比的增加（P<0.05）。与NT大鼠相比，从未治疗的HT大鼠分离的Langendorff心脏中，仅观察到对缓激肽的微弱冠状动脉扩张。赖诺普利使这种反应略有改善，而奥美沙坦酯使其显著改善（P<0.05）。在4周龄HT大鼠中降低的对硝普钠的冠状动脉扩张，经奥美沙坦酯治疗部分改善，但赖诺普利未使其改善。HT大鼠主动脉中超氧阴离子产生的增加，用奥美沙坦酯和赖诺普利部分纠正。最后，与赖诺普利不同，奥美沙坦酯显著降低了更严重形式的DOCA-盐高血压的死亡率。
奥美沙坦酯和赖诺普利使DOCA-盐高血压大鼠的冠状动脉重塑和心脏胶原沉积消退，并降低血管氧化应激。然而，尽管降压疗效相似，但奥美沙坦酯在改善内皮依赖性冠状动脉扩张方面优于赖诺普利，提示在DOCA-盐高血压模型中具有更好的血管保护作用。
