Abstract 479: Shortening of Mitochondria and Dilation of Endoplasmic Reticulum in the Medullary Thick Ascending Limb of Dahl Salt-Sensitive Rats

Abstract

Functional abnormalities in the kidney appear to precede or coincide with the initiation of salt-induced hypertension in the Dahl salt-sensitive SS rat. However, the structural basis or mechanism of early renal abnormalities, especially in the renal tubules, is poorly understood. We performed electron microscopy analysis in 7 week old SS rats and salt-insensitive consomic SS.13 BN rats and Sprague-Dawley (SD) rats fed a 4% NaCl diet for 7 days. Long mitochondria (>2 μm), an indication of healthy mitochondria, accounted for a significantly smaller fraction of all mitochondria in medullary thick ascending limbs in SS rats (4% ± 1%) than in SS.13 BN rats (8% ± 1%, P<0.05 vs. SS) and SD rats (9% ± 1%, P<0.01 vs. SS). This is consistent with our previous findings of mitochondrial insufficiency in the medulla of SS rats. Long mitochondria in proximal tubules, however, were more abundant in SS rats than in SS.13 BN and SD rats. The width of endoplasmic reticulum, an index of endoplasmic reticulum stress, was significantly greater in medullary thick ascending limbs of SS rats (107 ± 1 nm) than SS.13 BN rats (95 ± 2 nm, P<0.001 vs. SS) and SD rats (74 ± 3 nm, P<0.01 vs. SS or SS.13 BN ). The rat strain differences in ultrastructure were observed even though the tubules were indistinguishable by light microscopy and less than 5% of the kidney area was affected by inflammation, interstitial fibrosis, or tubular casts. These data indicate that ultrastructural abnormalities in the mitochondria and endoplasmic reticulum in the medullary thick ascending limbs occur in the early stage of, and could contribute to, the development of salt-induced hypertension.