Illustration of the interaction of PRR and PGs in the renal medulla during AngII-induced hypertension. Renin is expressed in the principal cells of the CD and its expression is induced by AngII. Prorenin and renin, released from the principalcells, bind PRR on the surface of intercalated cells or soluble PRR (sPRR) in the lumen to increase their catalytic activity. In the intercalated cells, AngII induces the expression of PRR that increases COX-2 expression via ERK1/2 and in turn COX-2-derived PGE2
via the EP4 receptor stimulates PRR expression, thus forming a vicious cycle in order to achieve the sustained activation of intrarenal RAS. This leads to heightened luminal AngII level that increases Na+ reabsorption possibly via increased ENaC activity, eventually leading to elevated blood pressure.