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(Circulation Research. 2007;100:556.)
© 2007 American Heart Association, Inc.

Cellular Biology

Connexin40 Is Essential for the Pressure Control of Renin Synthesis and Secretion

Charlotte Wagner^*, Cor de Wit, Lisa Kurtz, Christian Grünberger, Armin Kurtz, Frank Schweda^*

From the Physiologisches Institut der Universität Regensburg (C.W., L.K., C.G., A.K., F.S.), Germany; Physiologisches Institut der Universität Lübeck (C.d.W.), Germany.

Correspondence to Charlotte Wagner, PhD, Physiologisches Institut der Universität Regensburg, D-93040 Regensburg, Germany. E-mail charlotte.schmid{at}vkl.uni-regensburg.de

Renin secretion and synthesis in renal juxtaglomerular cells are controlled by short feed back loops involving angiotensin II and the intrarenal blood pressure. The operating mechanisms of these negative feed back regulators are widely unknown, except for the fact that both require calcium to exert their inhibitory action. We here show that in the absence of connexin40 (Cx40), which form gap junctions between juxtaglomerular and endothelial cells, the negative control of renin secretion and synthesis by angiotensin II and by intravasal pressure is abrogated, while the regulation by salt intake and ß-adrenergic stimulation is maintained. Renin secretion from Cx40-deficient kidneys or wild-type kidneys treated with the nonselective gap junction blocker 18-glycyrrhetinic acid (10 µmol/L) resembles the situation in wild-type kidneys in the absence of extracellular calcium. This disturbed regulation is reflected by an enhanced plasma renin concentration despite an elevated blood pressure in Cx40-deficient mice. These findings indicate that Cx40 connexins and likely intercellular communication via Cx40-dependent gap junctions mediate the calcium-dependent inhibitor effects of angiotensin II and of intrarenal pressure on renin secretion and synthesis. Because Cx40 gap junctions are also formed between renin producing cells and endothelial cells our finding could provide additional information to suggest that the endothelium may be strongly involved in the control of the renin system.

Key Words: gap junctions • connexin40 • renin • angiotensin II • perfusion pressure

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