부산대학교 도서관

Tubuloglomerular feedback (TGF)-mediated constriction of the afferent arteriole is modulated by a balance between release of superoxide ([O.sup.-.sub.2]) and nitric oxide (NO) in macula densa (MD) cells. Aldosterone activates mineralocorticoid receptors that are expressed in the MD and induces both NO and [O.sup.-.sub.2] generation. We hypothesize that aldosterone enhances [O.sup.-.sub.2] production in the MD mediated by protein kinase C (PKC), which buffers the effect of NO in control of TGF response. Studies were performed in microdissected and perfused MD and in a MD cell line, MMDD1 cells. Aldosterone significantly enhanced Of generation both in perfused MD and in MMDD1 cells. When aldosterone ([10.sup.-7] tool/l) was added in the tubular perfusate, TGF response was reduced from 2.4 [+ or -] 0.3 [micro]m to 1.4 [+ or -] 0.2 [micro]m in isolated perfused MD. In the presence of tempol, a [O.sup.-.sub.2] scavenger, TGF response was 1.5 [+ or -] 0.2 [micro]m. In the presence of both tempol and aldosterone in the tubular perfusate, TGF response was further reduced to 0.4 [+ or -] 0.2 [micro]m. To determine if PKC is involved in aldosterone-induced [O.sup.-.sub.2] production, we exposed the [O.sup.-.sub.2] cells to a nonselective PKC inhibitor chelerythrine chloride, a specific PKC[alpha] inhibitor Go6976, or a PKC[alpha] siRNA, and the aldosterone-induced increase in [O.sup.-.sub.2] production was blocked. These data indicate that aldosterone-stimulated [O.sup.-.sub.2] production in the MD buffers the effect of NO in control of TGF response, an effect that was mediated by PKC[alpha]. tubuloglomerular feedback; renal hemodynamics; nitric oxide; kidney doi: 10.1152/ajprenal.00501.2012