Komers Radko, Tian Wei, Lindsley Jessie N, Oyama Terry T, Cohen David M, Anderson Sharon
Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, and the Portland Veterans Affairs Medical Center, 97201-2940, USA.
J Lab Clin Med. 2002 Nov;140(5):351-7. doi: 10.1067/mlc.2002.128551.
COX-2-derived prostaglandins (PG) have been suggested to be important modulators of renin release and expression. However, the role of COX-2 in various high-renin states is still being debated. In the present studies we explored the role of COX-2-derived PG on basal and angiotensin converting enzyme inhibitor (ACEI)-stimulated plasma and renal renin concentrations (PRC and RRC, RIA), and mRNA expression (RmRNA, RNAse protection assay) in experimental diabetes (DM). Groups of moderately hyperglycemic (n = 5, approximately 350 mg/dl), streptozotocin-diabetic rats (D) after 3 weeks of DM were treated with a selective COX-2 inhibitor, MF-tricyclic (MF, 5 mg/kg/day for 10 days in food), the combination of MF and the ACEI enalapril (3 mg/kg/day), enalapril alone, or vehicle (MF-free chow), for 10 days. Non-diabetic control rats, fed MF-free chow, were also studied. All groups of diabetic rats demonstrated similar glycemic control. Treatment with ACEI resulted in significant elevations in PRC, RRC and RmRNA as compared to non-ACEI treated groups of diabetic and control rats. A similar rise in these parameters was observed in the rats treated with the combination of ACEI and MF. Furthermore, in diabetic rats treated with MF alone, PRC and RRC were similar to vehicle-treated animals. Diabetic rats demonstrated higher urinary PG as compared to controls. MF-treated rats demonstrated a significant reduction in urinary PG excretion. In summary, selective COX-2 inhibition influenced neither basal renin status nor ACEI-induced renin release and expression in diabetic rats. These findings do not support a significant role for COX-2 in mediating renin status in diabetes.
环氧合酶-2（COX-2）衍生的前列腺素（PG）被认为是肾素释放和表达的重要调节因子。然而，COX-2在各种高肾素状态中的作用仍存在争议。在本研究中，我们探讨了COX-2衍生的PG对基础状态以及血管紧张素转换酶抑制剂（ACEI）刺激后的血浆和肾脏肾素浓度（PRC和RRC，放射免疫分析法），以及实验性糖尿病（DM）中mRNA表达（RmRNA，核糖核酸酶保护分析法）的作用。将中度高血糖（n = 5，约350 mg/dl）、链脲佐菌素诱导糖尿病3周后的大鼠（D）分为几组，分别用选择性COX-2抑制剂MF-三环类药物（MF，5 mg/kg/天，在食物中给药10天）、MF与ACEI依那普利联合用药（3 mg/kg/天）、单独使用依那普利或赋形剂（不含MF的食物）处理10天。还研究了喂食不含MF食物的非糖尿病对照大鼠。所有糖尿病大鼠组的血糖控制情况相似。与未用ACEI处理的糖尿病和对照大鼠组相比，ACEI治疗导致PRC、RRC和RmRNA显著升高。在接受ACEI和MF联合治疗的大鼠中，这些参数也有类似升高。此外，单独用MF治疗的糖尿病大鼠，PRC和RRC与用赋形剂处理的动物相似。与对照组相比，糖尿病大鼠的尿PG水平更高。用MF治疗的大鼠尿PG排泄显著减少。总之，选择性COX-2抑制对糖尿病大鼠的基础肾素状态以及ACEI诱导的肾素释放和表达均无影响。这些发现不支持COX-2在介导糖尿病肾素状态中起重要作用。
