Blood pressure centrally controls renal renin release and synthesis. The precise operating mechanisms of this renal baroreceptor mechanism are widely unknown. We investigated the role of intercellular communication in this process by using mice with a genetic deletion of connexin40, which forms gap junctions between the reninproducing juxtaglomerular and their neighboring cells. Cx40-/- mice are hypertensive (150+4.1mmHg; Cx40+/+ 124.4+4.5mmHg), have elevated plasma renin concentrations (PRC; 5-fold vs. Cx40+/+) and renal renin gene expression levels (2.4-fold vs. Cx40+/+). 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 elevations 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+/+ a reduction of perfusion pressure stimulated renin secretion while an increase in perfusion pressure suppressed it. This inverse relationship between pressure and renin release was absent in kidneys of Cx40-/- or in wildtype kidneys after pharmacological blockade of gap junctions. In conclusion intercellular communication within the juxtaglomerular apparatus via connexin40 is critical for the pressure control of the renin system.