Restoring a Critical Element in Renin-Producing Cells

Abstract

See related article, pp 1198–1204 The kidney is crucial for arterial pressure control, and this key function is exerted in part by 1 of its endocrine functions—the release of the protease renin. It is released by specialized juxtaglomerular cells in afferent arterioles (renin-producing cells, RPCs), and the release is governed mainly by the activity of the sympathetic system, by the chloride content in the fluid of the distal tubule at the macula densa, and by renal perfusion pressure. Appropriate secretion of renin into the blood stream requires a close interaction of many cells, possibly even different cell types, and therefore intercellular communication is a prerequisite. This can be achieved by the release of mediators but also by direct communication through gap junction channels composed of connexins. In recent years, it has emerged that of this protein family, specifically connexin40 (Cx40) is crucially involved. Global deletion of Cx40 (Cx40-null mice) induces hypertension and enhances renin release by disrupting the negative feedback of pressure on RPCs.1,2 Cx40 is expressed in endothelial cells (ECs) as well as in RPCs and may also interconnect these cell types. However, cell-selective deletion demonstrated that Cx40 is necessary in RPC but not in ECs to exert this feedback.3,4 Only mice deficient for Cx40 in RPCs were hypertensive and exhibited enhanced renin levels, whereas EC-deficient mice were normotensive. Despite this seemingly good evidence, doubts remain as hypertension itself or the deficiency of a single member of the Cx family may alter the expression of other Cx as was reported for Cx37.4–6 In this issue of Hypertension …