Abstract 062: Renal Hydrogen Peroxide Prevents Salt-Sensitive Hypertension

Abstract

C57Bl/6 and BALB/c are different in the sensitivity of their blood pressure (BP) to NaCl. High NaCl diet increases BP in C57Bl/6J but not BALB/c mice. However, C57Bl/6J mice are less prone to hypertension-induced renal injury than other mouse strains. The goal of this study was to determine the role of H 2 O 2 in salt-sensitive hypertension. Basal renal levels of reactive oxygen species, including H 2 O 2, were higher in BALB/c renal proximal tubule cells (RPTC-BALB/c) than RPTCs from C57Bl/6J mice (RPTC-C57Bl/6J) (60.8 ± 5 % vs 41.8 ± 12 %, n=8, P<0.03). Incubation media with 170 mM NaCl (HS) increased H 2 O 2 production in RPTC-BALB/c but not in RPTC-C57Bl/6J, compared with RPTCs incubated in low (90 mM) or normal (145 mM) NaCl (+68±43%, 90 vs 170 mM, n=7, P<0.05). H 2 O 2 (10 μM) treatment of the basolateral side of RPTC-BALB/c in Transwells increased intracellular Na + 1.62-fold that of vehicle-treated cells (n=4, P<0.05). Over-expression of catalase, abrogated the H 2 O 2 -induced increase in intracellular Na + in RPTC-BALB/c. Over-expression of catalase in the kidneys of BALB/c mice on normal (0.9%) NaCl diet did not alter their SBP. However, on high (4%) NaCl diet, SBP was increased in catalase over-expressing mice, relative to vehicle-treated controls (98±1.1 vs 112±1.4 mm Hg, n=3, P<0.05). Decreasing H 2 O 2 by overexpression of catalase predisposes BALB/c mice to salt-sensitive hypertension, suggesting that high salt-induced H 2 O 2 negatively regulates renal sodium transport and provides resistance to salt-induced hypertension.