Li P, Jackson E K
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Life Sci. 1987 Oct 19;41(16):1903-8. doi: 10.1016/0024-3205(87)90741-7.
Converting enzyme inhibitors prevent the development of hypertension and normalize arterial blood pressure in spontaneously hypertensive rats (SHR), suggesting a critical role for angiotensin II in genetic hypertension. We hypothesized that the SHR is hyperresponsive to the slow-pressor effect of angiotensin II. To test this hypothesis, 14 SHR and 14 normotensive Wistar Kyoto rats (WKY) were treated chronically with captopril (100 mg X kg-1 X day-1 in drinking water) beginning at 5 weeks of age. At 9 weeks of age, either angiotensin II (125 ng/min; 7 SHR and 7 WKY) or vehicle (7 SHR and 7 WKY) was infused for 2 weeks via an osmotic minipump implanted into the peritoneal cavity. Captopril treatment was maintained and systolic blood pressure was monitored 3 times weekly. Although systolic blood pressure was similar in SHR and WKY infused with vehicle (101 +/- 2 versus 103 +/- 5 mmHg, respectively during the second week), systolic blood pressure in SHR treated with angiotensin II was much greater than systolic blood pressure in WKY treated with angiotensin II (193 +/- 9 versus 132 +/- 11 mmHg, respectively during the second week, p less than 0.001). These results indicate that compared to WKY, SHR are remarkably more sensitive to the slow-pressor effect of chronic, low-dose infusions of angiotensin II. Our results support the hypothesis that the critical genetic defect in SHR is a change in the sensitivity to the slow-pressor effect of angiotensin II.
转换酶抑制剂可预防高血压的发生，并使自发性高血压大鼠（SHR）的动脉血压恢复正常，这表明血管紧张素II在遗传性高血压中起关键作用。我们假设SHR对血管紧张素II的缓慢升压作用反应过度。为了验证这一假设，从5周龄开始，对14只SHR和14只血压正常的Wistar Kyoto大鼠（WKY）长期给予卡托普利（饮用水中100 mg·kg-1·天-1）。9周龄时，通过植入腹腔的渗透微型泵，对7只SHR和7只WKY输注血管紧张素II（125 ng/min）或赋形剂（7只SHR和7只WKY），持续2周。维持卡托普利治疗，并每周监测3次收缩压。尽管输注赋形剂的SHR和WKY的收缩压相似（第二周分别为101±2和103±5 mmHg），但接受血管紧张素II治疗的SHR的收缩压远高于接受血管紧张素II治疗的WKY的收缩压（第二周分别为193±9和132±11 mmHg，p<0.001）。这些结果表明，与WKY相比，SHR对慢性低剂量输注血管紧张素II的缓慢升压作用明显更敏感。我们的结果支持以下假设：SHR的关键基因缺陷是对血管紧张素II缓慢升压作用的敏感性发生改变。
