Intercellular communication between renin expressing As4.1 cells, endothelial cells and smooth muscle cells

Angiotensin II (AII) regulation of renin production by the juxtaglomerular (JG) cells of the kidney is commonly thought to occur through a direct feedback mechanism. However, recent evidence suggests that other cells in the vicinity may indirectly mediate AII's effect on renin production. Therefore we investigated whether an in vitro model of JG cells (As4.1) could have intercellular communication with endothelial or smooth muscle cells, which are in proximity to JG cells in vivo. 6-carboxyfluorescein was introduced to individual bovine aortic endothelial cells in co-culture with As4.1 cells. Coupling was observed 84% of the time at resting membrane potential and was attenuated by membrane depolarization or octanol (1 mM). Calcein green transfer between human aortic smooth muscle and As4.1 cells occurred 82% of the time and was inhibited by octanol. Expression of connexin 37, 40, 43, and 45 were detected in As4.1 cells using RT-PCR. Stimulation of As4.1 cells by AII failed to alter [Ca(2+)](i) or renin mRNA levels. These findings support the existence of gap junctions between renin producing cells and other cell types of the JG region. Moreover the lack of effect by AII suggest that feedback regulation of renin by AII may be due in part to intercellular communication with cells in proximity to JG cells.