Rumble J R, Komers R, Cooper M E
Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg, Australia.
J Hypertens. 1996 May;14(5):601-7. doi: 10.1097/00004872-199605000-00009.
To determine the roles played by kinins/nitric oxide and angiotensin II in the antitrophic effects of angiotensin converting enzyme inhibitors on mesenteric arteries after 3 weeks of streptozotocin diabetes by using blockers both of the angiotensin II AT1 receptor and of the bradykinin B2 receptor.
Male diabetic Wistar rats were randomly allocated to receive no treatment, the angiotensin converting enzyme inhibitors perindopril or ramipril, the AT1 receptor blocker ZD7155, the bradykinin B2 receptor blocker Hoe 140, the nitric oxide synthase inhibitor NG-nitro-L-arginine-methyl ester, concomitant administration of perindopril plus subcutaneous Hoe 140, perindopril plus NG-nitro-L-arginine, or ramipril plus Hoe 140 (Hoe 140 administered via an Alzet mini-osmotic pump).
After 3 weeks, the rats were killed, their blood collected and their mesenteric vessels removed. The mesenteric vascular weight was measured and the media wall: lumen area ratio was assessed using quantitative histomorphometric techniques.
Diabetes was associated with an increase in mesenteric weight and media wall:lumen area ratio. The angiotensin converting enzyme inhibitors, perindopril and ramipril, and the AT1 receptor antagonist ZD7155 reduced blood pressure and attenuated vascular weight and media wall:lumen area ratio. Concomitant administration of an angiotensin converting enzyme inhibitor with the kinin antagonist Hoe 140, administered either subcutaneously or via a mini-osmotic pump, or of the nitric oxide synthase inhibitor NG-nitro-L-arginine attenuated the effect of the angiotensin converting enzyme inhibitor on the mesenteric vascular weight and wall:lumen area ratios. Treatment with Hoe 140 or NG-nitro-L-arginine alone affected none of these parameters.
The antitrophic effect of angiotensin converting enzyme inhibitors on diabetic mesenteric arteries is mediated by inhibition of angiotensin II and by actions on the kinin-nitric oxide pathway.
通过使用血管紧张素II AT1受体阻滞剂和缓激肽B2受体阻滞剂，确定在链脲佐菌素诱导的糖尿病3周后，激肽/一氧化氮和血管紧张素II在血管紧张素转换酶抑制剂对肠系膜动脉的抗肥厚作用中所起的作用。
雄性糖尿病Wistar大鼠被随机分配接受以下处理：不治疗、血管紧张素转换酶抑制剂培哚普利或雷米普利、AT1受体阻滞剂ZD7155、缓激肽B2受体阻滞剂Hoe 140、一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯、培哚普利加皮下注射Hoe 140、培哚普利加NG-硝基-L-精氨酸，或雷米普利加Hoe 140（Hoe 140通过Alzet微型渗透泵给药）。
3周后，处死大鼠，采集血液并取出肠系膜血管。测量肠系膜血管重量，并使用定量组织形态计量学技术评估中膜壁：管腔面积比。
糖尿病与肠系膜重量增加以及中膜壁：管腔面积比增加有关。血管紧张素转换酶抑制剂培哚普利和雷米普利，以及AT1受体拮抗剂ZD7155降低了血压，并减轻了血管重量和中膜壁：管腔面积比。血管紧张素转换酶抑制剂与缓激肽拮抗剂Hoe 140（皮下或通过微型渗透泵给药）或一氧化氮合酶抑制剂NG-硝基-L-精氨酸联合给药减弱了血管紧张素转换酶抑制剂对肠系膜血管重量和壁：管腔面积比的作用。单独使用Hoe 140或NG-硝基-L-精氨酸处理对这些参数均无影响。
血管紧张素转换酶抑制剂对糖尿病肠系膜动脉的抗肥厚作用是通过抑制血管紧张素II以及对激肽-一氧化氮途径的作用介导的。
