Fang T C, Huang W C
Department of Internal Medicine, Tzu Chi General Hospital, and Graduate Institute of Medical Sciences, Tzu Chi College of Medicine and Humanities, Hualien, Taiwan, Republic of China.
J Hypertens. 1998 Dec;16(12 Pt 1):1767-74. doi: 10.1097/00004872-199816120-00009.
To investigate the role of angiotensin II in the pathogenesis of hyperinsulinemia-induced hypertension in rats.
Chronic hyperinsulinemia was achieved by infusing insulin (3 mU/kg per min) subcutaneously by an osmotic minipump for 6 weeks. An angiotensin converting enzyme inhibitor (fosinopril, 10 mg/kg per day) was added in drinking water and the angiotensin II subtype 1 receptor antagonist losartan (3.5 microg/kg per min) was co-infused via the minipump. Control rats were administered the vehicle only. The rats were housed in individual metabolic cages and fed a sodium-controlled diet. Food and water intake and urine output were measured daily. Systolic blood pressure and heart rate were measured by the tail-cuff method twice a week.
By the end of weeks 4 and 6 of the sustained insulin infusion, systolic blood pressure had increased significantly (P < 0.05), from 134+/-1 to 157+/-2 and 158+/-2 mmHg, respectively, and the heart rate had increased significantly (P< 0.05), from 380+/-9 to 423+/-7 and 426+/-6 beats/min, respectively. The plasma insulin concentration increased by 2-2.5 times but no significant changes in plasma glucose and triglyceride levels were noted. Concomitant treatment with fosinopril prevented the rises in systolic blood pressure and heart rate in the insulin-infused rats. When the insulin-induced hypertension had become established (systolic blood pressure increased from 132+/-3 to 155+/-2 mmHg 4 weeks after the infusion, P< 0.05 ), subsequent fosinopril or losartan treatment for 2 weeks reversed the elevated systolic blood pressure and heart rate to the control levels. There were no significant differences in water intake, urine flow, sodium gain and body weight gain between the control and the insulin-infused rats.
Angiotensin converting enzyme inhibition or angiotensin II type 1 receptor antagonism can prevent and reverse insulin-induced hypertension in rats, suggesting that angiotensin II itself or an angiotensin II-dependent mechanism has an etiological influence in the pathogenesis of this hypertension model.
研究血管紧张素II在大鼠高胰岛素血症诱导的高血压发病机制中的作用。
通过渗透微型泵皮下注射胰岛素（3 mU/kg每分钟）6周来实现慢性高胰岛素血症。在饮水中添加血管紧张素转换酶抑制剂（福辛普利，10 mg/kg每天），并通过微型泵共同输注血管紧张素II 1型受体拮抗剂氯沙坦（3.5微克/千克每分钟）。对照大鼠仅给予赋形剂。将大鼠饲养在单独的代谢笼中，并给予钠控制饮食。每天测量食物和水摄入量以及尿量。每周通过尾套法测量收缩压和心率两次。
在持续输注胰岛素的第4周和第6周结束时，收缩压显著升高（P < 0.05），分别从134±1升高到157±2和158±2 mmHg，心率也显著升高（P<0.05），分别从380±9升高到423±7和426±6次/分钟。血浆胰岛素浓度增加了2 - 2.5倍，但血浆葡萄糖和甘油三酯水平未发现显著变化。福辛普利联合治疗可防止胰岛素输注大鼠的收缩压和心率升高。当胰岛素诱导的高血压确立后（输注4周后收缩压从132±3升高到155±2 mmHg，P<0.05），随后给予福辛普利或氯沙坦治疗2周可使升高的收缩压和心率恢复到对照水平。对照大鼠和胰岛素输注大鼠在水摄入量、尿流量、钠摄入量和体重增加方面没有显著差异。
血管紧张素转换酶抑制或血管紧张素II 1型受体拮抗可预防和逆转大鼠胰岛素诱导的高血压，提示血管紧张素II本身或血管紧张素II依赖性机制在该高血压模型的发病机制中具有病因学影响。
