Skinner S, Bouhnik J, Huang H, Gonzalez M F, Ménard J, Corvol P
INSERM U367, Paris, France.
Clin Exp Hypertens. 1995 Jul;17(5):847-60. doi: 10.3109/10641969509033639.
Plasma renin-angiotensin parameters were measured before and 24h after binephrectomy (BNx) in male Swiss (Ren-1, Ren-2) and BALB/c (Ren-1) female mice (representing the extremes of differences in tissue renin expression), together with in vivo inhibition of residual renin. Plasma Ang II increased from 18.9 +/- 7.3 to 48.1 +/- 16.9 pg/ml after BNx in conscious Swiss mice (+/- sd, p < 0.001, n = 11&12), renin activity (PRA) increased 2.76 times, angiotensinogen (aogen) increased 4.57 times and renin concentration (PRC) fell by 65%. In BALB/c, Ang II+Ang III decreased slightly (56.6 +/- 11 to 37.7 +/- 14.7, p < 0.05, n = 5&6), PRA was unchanged, aogen increased 12 times and PRC fell by 93%. Plasma ACE decreased by 26% and 28% respectively. Aogen did not increase further when post BNx plasma renin was inhibited with antirenin in vivo during 20h. Thus plasma angiotensin is maintained or considerably increased following BNx in mice and the change is consistent with first-order kinetics with respect to renin and aogen in the circulation. Whether the strain carries one or two renin genes, high renal and extrarenal renin production combined with a low plasma aogen phenotype yields resting angiotensin levels similar to other mammals. A kinetic regulation of aogen levels is proposed in mice wherein Ang II production is limited by low substrate concentration thereby ensuring normotension in the face of abundant extrarenal renin secretion.
在雄性瑞士(Ren - 1、Ren - 2)和雌性BALB/c(Ren - 1)小鼠(代表组织肾素表达差异的极端情况)双侧肾切除(BNx)前及术后24小时测量血浆肾素 - 血管紧张素参数,并对残余肾素进行体内抑制。清醒的瑞士小鼠BNx后,血浆血管紧张素II(Ang II)从18.9±7.3 pg/ml增加至48.1±16.9 pg/ml(±标准差,p<0.001,n = 11&12),肾素活性(PRA)增加2.76倍,血管紧张素原(aogen)增加4.57倍,肾素浓度(PRC)下降65%。在BALB/c小鼠中,Ang II + Ang III略有下降(56.6±11至37.7±14.7,p<0.05,n = 5&6),PRA无变化,aogen增加12倍,PRC下降93%。血浆血管紧张素转换酶(ACE)分别下降26%和28%。在BNx后20小时用抗肾素体内抑制血浆肾素时,aogen未进一步增加。因此,小鼠BNx后血浆血管紧张素得以维持或显著增加,且这种变化与循环中肾素和aogen的一级动力学一致。无论该品系携带一个还是两个肾素基因,高肾性和肾外肾素产生与低血浆aogen表型相结合,产生的静息血管紧张素水平与其他哺乳动物相似。提出了小鼠中aogen水平的动力学调节机制,其中Ang II的产生受低底物浓度限制,从而在肾外肾素大量分泌的情况下确保血压正常。