卡托普利治疗自发性高血压大鼠对循环和局部肾素-血管紧张素系统的长期影响

The Long-term Effects of Captopril Treatment on Circulating and Tissue Reninangiotensin System in Spontaneously Hypertensive Rat

目的探讨卡托普利治疗自发性高血压大鼠（ＳＨＲ）对循环和局部肾素－血管紧张素系统（ＲＡＳ）的长期影响。方法雄性ＳＨＲ（ｎ＝４３）宫内期始，予卡托普利治疗（１００ｍｇ·ｋｇ－１·ｄ－１）到１６周，并分别在１６周（ｎ＝１９）和４０周（ｎ＝２４）处死，年龄、性别、数量配对的未治疗ＳＨＲ和Ｗｉｓｔａｒ－ｋｙｏｔｏ（ＷＫＹ）大鼠作对照。测定收缩压（ＳＢＰ）、左室重（ＬＶＭ）与体重（ＢＷ）比、左室心肌和血浆血管紧张素Ⅱ（ＡｎｇⅡ）浓度（放免测定法）、主动脉和血清血管紧张素转换酶（ＡＣＥ）活性（紫外分光光度法）、肾脏和肝脏血管紧张素原（ＡＧＴ）基因表达、肾脏肾素基因表达（ＮｏｒｔｈｅｒｎＢｌｏｔ）。结果卡托普利治疗显著降低ＳＨＲ１６周ＳＢＰ和ＬＶＭ／ＢＷ，并持续到４０周。治疗不影响ＢＷ、血浆ＡｎｇⅡ浓度、血清ＡＣＥ活性和肝脏ＡＧＴ基因表达，但明显减少ＳＨＲ４０周左室心肌ＡｎｇⅡ浓度，抑制ＳＨＲ１６周主动脉ＡＣＥ活性，并持续到４０周，减少ＳＨＲ１６周和４０周肾脏ＡＧＴ基因的表达，卡托普利治疗停药前肾脏肾素基因表达明显增强。结论长期卡托普利治疗ＳＨＲ，停药后长时间抑制组织的肾素－血管紧张素系统如心肌ＡｎｇⅡ生成、主动脉ＡＣＥ活?

Aim\ To investigate the chronic effect of captopril treatment on circulating and tissue renin-angiotensin system(RAS) in relation to left ventricular hypertrophy and blood pressure.\ Methods\ Male spontaneously hypertensive rates(SHR) were given captopril 100 mg·kg -1 ·d -1 (SHRcap n=43) from intrautero period to 16 weeks(wks) of age, then the treatment was removed.\ Rats were killed at 16(n=19) and 40(n=24) wks of age respectively.\ Male,agematched untreated SHR and WistarKyoto(WKY) rats served as controls.\ Systolic blood pressure(SBP), left ventricular mass/body weight(LVM/BW) ratio were determined.\ Left ventricular(LV) myocardium and plasma angiotensin Ⅱ(AngⅡ) concentration were assessed by radioimmunoassay.\ Aortic and serum angiotensin converting enzyme(ACE) activity were measured by spectrophotometric method.\ Angiotensinogen(AGT) mRNA level in kidney and liver, renal renin mRNA level were determined using Northern blot.\ Results\ Early captopril treatment significantly decreased SBP(mmHg:158±11 vs untreated SHR 216±12,P<005) and LVM/BW(mg/g:256±022 vs untreated SHR 355±023, P<005) at 16 wks of age, and the effect remained to 40 wks of age(SBP mmHg:173±10 vs untreated SHR 232±16 P<005; LVM/BW mg/g: 287±023 vs untreated SHR 375±052, P<005).\ Captopril therapy did not affect BW, plasma AngⅡ concentration, serum ACE activity and AGT mRNA in liver, but markedly reduced LV myocardium AngⅡ concentration at 40 wks of age(pg/100 mg: 263±64 vs untreated SHR 316±62, P<005), inhibited aortic ACE activity at 16 wks(U/100 g:46±15 vs untreated SHR 63±21, P<005) and 40 wks of age(U/100 g:71±16 vs untreated SHR 94±23, P<005); reduced 465%～511% AGT mRNA level in kidney of 16 wks and 40 wks SHR.\ Conclusion\ AGT mRNA in kidney, LV myocardium AngⅡ and aortic ACE activity, rather than AGT mRNA in liver, renin mRNA in kidney, plasma AngⅡ and serum ACE activity, could be inhibited by longterm captopril treatment, and it may play a role in the mechanisms of the persistent antihypertensive effect and preventive effect of LVH of captopril.