Who and where is the renal baroreceptor?: the connexin hypothesis

Abstract

Gap junctions are emerging as a fundamental mechanism for the control of renin synthesis and release. Connexin40 is prominent in juxtaglomerular cells. When missing, it results in hyperreninemia and hypertension. Schweda et al. offer exciting data demonstrating that connexin45, a connexin with different biophysical properties, can replace connexin40 functions related to the control of renin.

Figure 1. Response of renin cells to changes in perfusion pressure and angiotensin II in Cx40^−/− mice

Graphs relating renin-secreting rate (RSR) to perfusion pressure (PP) and to angiotensin II (Ang II) are adapted from Wagner et al. For comparison, the normal curves in wild-type animals (Cx40 ^+/+, blue) are also depicted. Cx40^−/− animals are hyperreninemic and hypertensive. Although plasma renin concentration and the response to several manipulations are normalized when Cx40 is replaced by Cx45, blood pressure improves, but it does not reach normal wild-type levels.

Figure 2. Renin distribution during ontogeny and recruitment

During embryonic development, renin cells (yellow, with black dots representing granules) are broadly distributed along intrarenal arteries, inside the glomeruli, and in the renal interstitium. With maturation the number of renin cells is progressively restricted to a few cells in the juxtaglomerular (JG) area of the adult kidney. The extension and localization of renin cells during recruitment in the adult vary depending on the physiological manipulation and the intensity and duration of the stimulus. Usually, the increase in the number of renin cells occurs along and upstream of the afferent arteriole. Recruited cells can also be observed in the intraglomerular mesangium, extraglomerular mesangium, interstitium, and occasionally the glomerular capsule and efferent arteriole.