Ultrastructural changes associated with renin secretion from the juxtaglomerular apparatus of mice

Abstract

Thin sections and freeze-fracture replicas were used to investigate the ultrastructural changes associated with renin secretion from the juxtaglomerular part of the afferent arteriole of male mice. Adrenalectomized animals in which renin secretion was stimulated by furosemide application and bleeding were also studied. Exocytosis of mature electron-dense granules was found in all experimental groups. Before extrusion, the region of granule facing the cell membrane changed, with vesicular and/or stacked membrane-like profiles and a small local protrusion of the granule membrane appearance of. Concomitantly, punctuate sites of fusion between the cell and granule membranes were observed. Later, unaltered amorphous, and altered membrane-like granule content was released from omega-shaped cavities into the extracellular space. In stimulated animals the alteration and extrusion of several closely apposed granules was reminiscent of compound exocytosis. Coated pits were frequently seen, suggesting specific retrieval of the former granule membrane. The collapsing silhouette of a depleted granule very rarely took the form of a saccule whose narrow membrane-bounded neck was continuous with the extracellular space. Observed were two additional events by which active and inactive renin may be released. Small electron-lucent vacuoles of undetermined origin fused with the cell membrane and, in stimulated kidneys, some epithelioid cell processes disintegrated. However, the interpretation of the related ultrastructural phenomena was uncertain.

Endothelial cell-specific knockout of connexin 43 causes hypotension and bradycardia in mice

“…It seems most likely that the elevated Ang II may be a compensatory response to an initial blood pressure drop induced by NO. We note, however, that Cx43 might be more directly involved in the control of renin secretion from the juxtaglomerular apparatus (JGA) because Cx43 proteins are extremely abundant in kidney (26,27), where gap junctional communication is extensive, including connections between VSM and endothelium (20). Thus, the deletion of Cx43 in the endothelium might inhibit the communication between endothelium and JGA and result in an altered secretion of renin.…”

“…The VSM and endothelium of the afferent arterioles are extensively connected by gap junctions, and this is a site of very dense gap junctional plaque formation (20). We therefore assessed plasma Ang I and II concentration.…”

Connexin43-dependent mechanism modulates renin secretion and hypertension

“…This control is mostly achieved by the juxtaglomerular apparatus, which accommodates, in small regions of the kidney, several cell types, including smooth muscle, endothelial, mesangial, macula densa, and renin-producing cells of the afferent arterioles. Cells of each type are connected by gap junctions (16)(17)(18)(19)(20)(21)(22), and other gap junctions further link the ECs, the smooth muscle cells, and the renin-producing cells of the afferent arteriole (19,23,24). Connexin43 (Cx43) and Cx40 appear to be the prominent connexins forming these junctions in vivo (22,23).…”

Ren-1 and Ren-2 loci are expressed in mouse kidney.

“…In the kidney, renin is synthesized in the juxtaglomerular cells, which constitute <1% of cells of this organ (this figure is obtained by dividing the estimated number ofjuxtaglomerular cells by the estimated number of cells per kidney; ref. 5). When transcript accumulation is normalized to the number of cells synthesizing renin, we see that Ren-2 transcript accumulation in the SMG granular convoluted tubule cells is roughly equivalent to the composite renin transcript accumulation in the kidney juxtaglomerular cells (Table 1).…”