Gap junctional communication via connexin40 is essential for the pressure control of the renin system

Although the regulation of renin release and synthesis in renal juxtaglomerular cells by the blood pressure is known since decades the precise operating mechanisms of this renal baroreceptor mechanism are widely unknown. In the present study we investigated the role of intercellular communication in this process by the use of mice with a genetic deletion of connexin40, which forms gap junctions between juxtaglomerular and endothelial cells. Cx40−/− mice are hypertensive (150+4.1mmHg; Cx40+/+ 124.4+4.5mmHg), have elevated plasma renin concentrations (PRC) and renal renin gene expression levels. Clipping of the left renal artery for one week elevated blood pressure (+32mmHg), PRC (3.4‐fold) and renal renin mRNA expression (8.2‐fold, ratio clipped/unclipped kidney) in Cx40+/+. In contrast, the elevation of blood pressure and PRC were blunted and renal renin mRNA expression was only slightly stimulated (2.2‐fold) by renal artery clipping in Cx40−/−. In isolated perfused kidneys of Cx40+/+ the known inverse relationship between perfusion pressure and renin secretion rates was observed. This inverse relation was completely absent in kidneys of Cx40−/− or wildtype kidneys in the presence of the gap junction blocker 18alpha‐glycyrrhetinic acid, underlining the conclusion that intercellular communication via Cx40‐dependent gap junctions is critical for the pressure dependent regulation of the renin system.