Abstract 320: Renal Responses to Nitric Oxide Synthase Inhibition during High Salt Intake in Gp91phox Knockout Mice
It was reported that high salt (HS) intake enhanced superoxide (O2−) production as well as nitric oxide (NO) synthase activity in the short term (within a week) though the later decreased with the long term HS intake. We hypothesized that a differential regulation of kidney function exists between short term and long term HS intake that depends on the concomitant activation of the NO and O2− generating systems. To examine this, we assessed the basal values and the responses to acute NO inhibition (i.v. infusion of L-NAME; 0.2μg/g/min for more than 60 min) on renal hemodynamics and excretory function in Gp91phox (subunit of NADPH oxidase) knockout (KO) mice subjected to HS intake (4% NaCl in diet) for 4–5 days (short term) and 13–14 days (long term) and compared these responses with those in the corresponding wild type (WT) mice. Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by standard PAH and Inulin clearance techniques respectively. In WT mice, basal RBF (8.5 ±0.5 mL/min/g) and GFR (1.05 ±0.05 mL/min/g) during short term HS intake (n=8) were higher (p< 0.05) than those during long term HS intake (5.8 ±0.8 and 0.80 ±0.05 mL/min/g, respectively; n=8). In KO mice, basal RBF (6.6 ±0.4 and 6.5 ±0.4 mL/min/g) and GFR (0.75 ±0.05 and 0.74 ±0.05 mL/min/g) were similar during both short (n=7) and long term HS intake (n=7). In response to L-NAME in WT mice, greater reduction in RBF (45 ±4 % vs 29 ±6%) was observed in short term than in long term HS intake but the reductions were similar in both conditions in KO mice (30 ±8% vs 36 ±5%). In WT, L-NAME decreased GFR in short term (26 ±4%; p< 0.05) but not in long term (5 ±6%; p=n.s.) HS intake. However, GFR reduction in response to L-NAME in KO mice was greater (p< 0.05) in long term (37 ±4%) than in short term (17 ±6%) HS intake. The increments in arterial pressure as well as the diuretic and natriuretic responses to systemic infusion of L-NAME were not statistically different between these strains. These data suggest that an enhancement of NO activity helps to regulates renal hemodynamics and excretory function in the condition of increased O2− production in response to HS intake. These data also indicate that the maintenance of GFR during long term HS intake is largely dependent on enhanced NO activity.