Superoxide and hydrogen peroxide stimulate renin release from juxtaglomerular cells

Abstract

Renin is the rate‐limiting enzyme in angiotensin formation, playing a pivotal role in blood pressure regulation. In the kidney, superoxide and hydrogen peroxide (H202) are involved in the development of hypertension by affecting nephron transport and vascular reactivity. However, it is not known whether superoxide and H202 are endogenously produced in juxtaglomerular (JG) cells, the source of these reactive oxygen species and whether they regulate renin release. We hypothesized that superoxide and H2O2 are endogenously produced in JG cells and that they stimulate renin release. Primary cultures of mouse JG cells were treated for 60 min with different inhibitors and renin released to the supernatant measured by radioimmunoassay. Decreasing endogenous superoxide with superoxide dismutase (300U/ml) inhibited renin release by 35±10% (p<0.03). By Western Blot we found that NOX4, one of the NADPH oxidase isoforms is present in JG lysates (n=3). Apocynin (120 μM), a general inhibitor of NADPH oxidases, decreased renin release by 28±7% (p<0.04). Since dismutation of superoxide results in H202 accumulation, we tested the effect of scavenging endogenous H202. Adding catalase (100U/ml) inhibited renin release by 37±10% (p<0.02). We concluded that endogenous superoxide and H202 stimulate renin release from mouse JG cells. These are the first data identifying endogenous sources of superoxide in JG cells. HFHS Award.