Angiotensin II Short-Loop Feedback Is There a Role of Ang II for the Regulation of the Renin System In Vivo?

作者：Neubauer Bjoern^*; Schrankl Julia; Steppan Dominik; Neubauer Katharina; Sequeira Lopez Maria Luisa; Pan Li; Gomez R Ariel; Coffman Thomas M; Gross Kenneth W; Kurtz Armin; Wagner Charlotte

来源：Hypertension, 2018, 71(6): 1075-1082.

DOI：10.1161/HYPERTENSIONAHA.117.10357

• AT(1) receptor
• kidney
• mice
• renin

The activity of the renin a Ootensin aldosterone system is triggered by the release of the protease renin from the kidneys, which in turn is controlled in the sense of negative feedback loops, It is widely assumed that Ang II (angiotensin II) directly inhibits renin expression and secretion via a short-loop feedback by an effect on renin-producing cells (RPCs) mediated by AT(1) (Aug II type 1) receptors. Because the concept of such a direct short-loop negative feedback control, which originates mostly from in vitro experiments, has not yet been systematically proven in vivo, we aimed to test the validity of this concept by studying the regulation of renin synthesis and secretion in mice lacking Aug II-AT(1) receptors on RPCs. We found that RPCs of the kidney express Ang II-AT(1) receptors. Mice with conditional deletion of Ang II-AT, receptors in RPCs were normal with regard to the number of renin cells, renal renin mRNA, and plasma renin concentrations. Renin expression and secretion of these mice responded to Ang I (angiotensin I) converting enzyme inhibition and to Ang II infusion like in wild-type (WT) controls. In summary, we did not obtain evidence that Ang II-AT(1) receptors on RPCs arc of major relevance for the normal regulation of renin expression and secretion in mice. Therefore, we doubt the existence of a direct negative feedback function of Ang II on RPCs.

• 出版日期2018-6