Department of Pharmacology, L. M. College of Pharmacy , Ahmedabad, Gujarat , India.
Clin Exp Hypertens. 2014;36(8):557-66. doi: 10.3109/10641963.2014.881842. Epub 2014 Feb 3.
Telmisartan possesses endothelial protective effects due to angiotensin II type 1 receptor antagonist, peroxisome proliferator-activated receptor γ (PPARγ) agonist and antioxidant action. Therefore, our objective was to study effect of telmisartan on angiogenic responsiveness of coronary endothelial cells (cECs) of normal and diabetic rats. Male Wistar rats were divided into six groups, normal rats, diabetic rats 30 d. (30 days after administration of STZ), diabetic rats 60 ds. (60 days after administration of STZ), telmisartan-treated normal rats (2 mg/kg, p.o., for 15 days before isolation of hearts), telmisartan-treated diabetic rats 30 ds, and telmisartan-treated diabetic rats 60 ds. Each group was further divided into two subgroups, sham rat hearts and ischemia-reperfused rat hearts. After isolation of cEC from each subgroup, angiogenic responsiveness and nitric oxide releasing properties were studied using chorioallantoic membrane (CAM) assay and Griess method, respectively. cEC of normal rats showed significant increase in angiogenic responsiveness in presence of vascular endothelial growth factor (VEGF) but not in absence of it. This activity was attenuated by pretreatment of cEC with l-NAME, wortmannin and chelerythrine. Diabetes and ischemia reperfusion injury suppressed angiogenic responsiveness of cEC. Telmisartan treatment showed significant increase in VEGF-induced angiogenic responsiveness and nitric oxide releasing properties of cECs of all subgroups as compared to their respective non-treated subgroups. These effects of telmisartan were significantly inhibited by pretreatment of cECs with L-NAME and wortmannin but not with chelerythrine. Our data suggest that telmisartan improves VEGF-induced coronary angiogenic activity in normal and diabetic rats via stimulation of PI3K/eNOS/NO pathway.
替米沙坦具有血管紧张素 II 型 1 型受体拮抗剂、过氧化物酶体增殖物激活受体 γ（PPARγ）激动剂和抗氧化作用，因此具有内皮保护作用。因此，我们的目的是研究替米沙坦对正常和糖尿病大鼠冠状动脉内皮细胞（cEC）血管生成反应的影响。雄性 Wistar 大鼠分为六组：正常大鼠、糖尿病大鼠 30d（STZ 给药后 30 天）、糖尿病大鼠 60d（STZ 给药后 60 天）、替米沙坦治疗正常大鼠（2mg/kg，po，在心脏分离前 15 天）、替米沙坦治疗糖尿病大鼠 30d 和替米沙坦治疗糖尿病大鼠 60d。每组进一步分为两个亚组：假手术大鼠心脏和缺血再灌注大鼠心脏。从每个亚组分离 cEC 后，使用绒毛尿囊膜（CAM）测定法和 Griess 法分别研究血管生成反应性和一氧化氮释放特性。正常大鼠的 cEC 在血管内皮生长因子（VEGF）存在下表现出明显的血管生成反应性增加，但在不存在 VEGF 的情况下则没有。该活性被 cEC 用 l-NAME、wortmannin 和 chelerythrine 预处理所减弱。糖尿病和缺血再灌注损伤抑制 cEC 的血管生成反应性。与各自的未处理亚组相比，替米沙坦治疗显着增加了所有亚组的 VEGF 诱导的血管生成反应性和 cECs 的一氧化氮释放特性。替米沙坦的这些作用被 cEC 用 l-NAME 和 wortmannin 预处理而不是 chelerythrine 预处理显著抑制。我们的数据表明，替米沙坦通过刺激 PI3K/eNOS/NO 途径改善正常和糖尿病大鼠的 VEGF 诱导的冠状动脉血管生成活性。
