Schricker K, Hegyi I, Hamann M, Kaissling B, Kurtz A
Physiologisches Institut der Universität Regensburg, Germany.
Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):8006-10. doi: 10.1073/pnas.92.17.8006.
This study was designed to examine the possible involvement of prostaglandins and nitric oxide (NO) in the renin stimulatory effect of angiotensin II (AngII) antagonists. To this end, plasma renin activities (PRAs) and renal renin mRNA levels were assayed in rats that were treated with the Ang-converting enzyme inhibitor ramipril or with the AngII AT1-receptor antagonist losartan. Ramipril and losartan increased PRA values from 7.5 +/- 1.6 to 86 +/- 6 and 78 +/- 22 ng of AngI per h per ml and renin mRNA levels from 112 +/- 9% to 391 +/- 20% and 317 +/- 10%, respectively. Inhibition of prostaglandin formation with indomethacin did not influence basal or ramipril-affected PRA. Basal renin mRNA levels also were unchanged by indomethacin, while increases in renin mRNA levels after ramipril treatment were slightly reduced by indomethacin. Inhibition of NO synthase by nitro-L-arginine methyl ester (L-NAME) reduced PRA values to 3.2 +/- 0.9, 34 +/- 13, and 12.1 +/- 2.7 ng of AngI per h per ml in control, ramipril-treated, and losartan-treated animals, respectively. Renin mRNA levels were reduced to 77 +/- 14% under basal conditions and ramipril- and losartan-induced increases in renin mRNA levels were completely blunted after addition of L-NAME. The AngII antagonists, furthermore, induced an upstream recruitment of renin-expressing cells in the renal afferent arterioles, which was also blunted by L-NAME. These findings suggest that renin mRNA levels are tonically increased by NO and that the action of NO is counteracted by AngII.
本研究旨在探讨前列腺素和一氧化氮（NO）在血管紧张素II（AngII）拮抗剂的肾素刺激作用中可能发挥的作用。为此，在分别用血管紧张素转换酶抑制剂雷米普利或AngII AT1受体拮抗剂氯沙坦治疗的大鼠中，测定了血浆肾素活性（PRA）和肾脏肾素mRNA水平。雷米普利和氯沙坦分别使PRA值从7.5±1.6增加到86±6和78±22 ng AngI/（h·ml），肾素mRNA水平从112±9%增加到391±20%和317±10%。用吲哚美辛抑制前列腺素形成对基础PRA或雷米普利影响的PRA没有影响。吲哚美辛也未改变基础肾素mRNA水平，而雷米普利治疗后肾素mRNA水平的增加则因吲哚美辛而略有降低。用硝基-L-精氨酸甲酯（L-NAME）抑制一氧化氮合酶后，对照组、雷米普利治疗组和氯沙坦治疗组的动物PRA值分别降至3.2±0.9、34±13和12.1±2.7 ng AngI/（h·ml）。在基础条件下，肾素mRNA水平降至77±14%，加入L-NAME后，雷米普利和氯沙坦诱导的肾素mRNA水平增加完全被抑制。此外，AngII拮抗剂诱导肾传入小动脉中肾素表达细胞向上游募集，这也被L-NAME抑制。这些发现表明，NO可使肾素mRNA水平持续升高，且AngII可抵消NO的作用。
