DeForrest J M, Knappenberger R C, Antonaccio M J, Ferrone R A, Creekmore J S
Am J Cardiol. 1982 Apr 21;49(6):1515-7. doi: 10.1016/0002-9149(82)90373-3.
The current study was undertaken to define the role of the renin-angiotensin system in the development of hypertension in the two kidney, one clip Goldblatt rat. Captopril was administered orally (100 mg/kg/day) to two groups of rats (n = 8 each) 24 hours before and each day after unilateral renal artery clipping (0.2 mm internal diameter): the drug was given for either 16 weeks (group I) or 24 weeks (group II). Sham-operated (n = 5) and Goldblatt (n = 8) rats not receiving captopril were prepared for comparisons of plasma renin activity and systolic blood pressure. Indomethacin (20 mg/kg/day subcutaneously) was administered for 48 hours concomitantly with captopril to the rats in group I. In group II, systolic blood pressure was monitored for 7 weeks after cessation of captopril. Continual captopril administration to Goldblatt rats completely prevented the rise in systolic blood pressure, a rise that was observed in Goldblatt rats not receiving captopril. Whereas systolic blood pressure of captopril-treated rats approximated 100 mm Hg throughout the study, that of Goldblatt rats not receiving the drug increased to nearly 180 mm Hg within 6 weeks after clipping. Systolic blood pressure of sham-operated rats remained normal. Indomethacin did not change systolic blood pressure in the drug-treated rats in group I. On cessation of captopril therapy in group II, systolic blood pressure increased gradually in a manner that paralleled the development of the disease in the Goldblatt rats that did not receive captopril. Plasma renin activity was determined in Goldblatt and sham-operated rats at either 16 weeks (group I) or 24 weeks (group II) after clipping; the rats from either group with mild hypertension (systolic blood pressure less than 180 mm Hg) had normal plasma renin activity whereas those with severe hypertension (systolic blood pressure greater than 180 mm Hg) had greatly elevated plasma renin activity. In summary, captopril can completely prevent the increase in systolic blood pressure for up to 24 weeks in Goldblatt rats, and this hypotensive effect is not mediated by the prostaglandins. It is concluded that the renin-angiotensin system is a necessary component of the hypertensive process in this experimental model.
本研究旨在确定肾素 - 血管紧张素系统在两肾一夹型戈德布拉特（Goldblatt）大鼠高血压发生过程中的作用。在单侧肾动脉夹闭（内径0.2毫米）前24小时及夹闭后每日，对两组大鼠（每组n = 8）口服卡托普利（100毫克/千克/天）：药物给药16周（I组）或24周（II组）。制备假手术组（n = 5）和未接受卡托普利的戈德布拉特大鼠（n = 8），以比较血浆肾素活性和收缩压。在I组大鼠中，吲哚美辛（20毫克/千克/天，皮下注射）与卡托普利同时给药48小时。在II组中，在停止卡托普利给药后监测收缩压7周。持续给戈德布拉特大鼠服用卡托普利可完全防止收缩压升高，而未接受卡托普利的戈德布拉特大鼠则出现收缩压升高。在整个研究过程中，接受卡托普利治疗的大鼠收缩压接近100毫米汞柱，而未接受该药物的戈德布拉特大鼠在夹闭后6周内收缩压升高至近180毫米汞柱。假手术大鼠的收缩压保持正常。吲哚美辛未改变I组接受药物治疗大鼠的收缩压。在II组停止卡托普利治疗后，收缩压逐渐升高，其方式与未接受卡托普利的戈德布拉特大鼠疾病发展过程相似。在夹闭后16周（I组）或24周（II组）测定戈德布拉特大鼠和假手术大鼠的血浆肾素活性；两组中轻度高血压（收缩压低于180毫米汞柱）的大鼠血浆肾素活性正常，而重度高血压（收缩压高于180毫米汞柱）的大鼠血浆肾素活性大幅升高。总之，卡托普利可在长达24周的时间内完全防止戈德布拉特大鼠收缩压升高，且这种降压作用不是由前列腺素介导的。得出的结论是，在该实验模型中，肾素 - 血管紧张素系统是高血压过程的必要组成部分。
