The aims of the present study were to determine whether superoxide (O 2-) production is enhanced in medullary thick ascending limb (mTAL) of Dahl salt-sensitive (SS) rats compared with a salt-resistant consomic control strain (SS.13BN) and to elucidate the cellular pathways responsible for augmented O2- production. Studies were carried out in 7- to 10-wk-old male SS and SS.13BN rats fed either a 0.4% NaCl diet or a 4.0% NaCl diet for 3 days before tissue harvest. Tissue strips containing mTAL were isolated from the left kidney, loaded with the O2--sensitive fluorescent dye dihydroethidium, superfused with modified Hanks' solution, and imaged at X60 magnification on a heated microscope stage. O2- production was stimulated in mTAL by incrementing superfusate NaCl concentration from 154 to 254 to 500 mM. O2- production was enhanced in mTAL of SS rats compared with SS.13BN rats in response to incrementing bath NaCl. Addition of N-methyl-amiloride (100 μM) or inhibition of NAD(P)H oxidase reduced O 2- production in SS mTAL to levels observed in SS.13 BN rats. Both amiloride- and ouabain-sensitive pathways of O 2- production were elevated following 3 days of high (4.0%) NaCl feeding in mTAL of SS and SS.13BN rats. We conclude that mTAL from SS rats exhibit enhanced amiloride-sensitive O2- production. The amiloride-sensitive O2- response in mTAL is independent of active Na+ transport and appears to be mediated by NAD(P)H oxidase. Amiloride-sensitive O2- production is likely to contribute to augmented outer medullary O2- production observed in SS rats during both normal and high NaCl diets.
- Blood pressure
- Free radicals
- Reduced nicotinamide adenine dinucleotide phosphatase oxidase
ASJC Scopus subject areas