Stretch Increases Intracellular Calcium More in Dahl‐Salt‐Sensitive than Salt‐Resistant Rat Thick Ascending Limbs

The thick ascending limb (TAL) reabsorbs 30 % of the filtered NaCl. It plays a pivotal role in the regulation of salt homeostasis and abnormal reabsorption of NaCl in this segment causes salt‐sensitive hypertension. We have shown that flow‐induced stretch stimulates superoxide production. Cellular stretch increases intracellular calcium (Ca i ) in other cells and Dahl salt‐sensitive rat (SS) TALs produce more superoxide than those from salt‐resistant rats (SR). Thus we hypothesized that mechanical stretch of SS TALs induces greater increases in Ca i than in SR TALs. We measured Ca i using the ratiometric calcium‐sensitive dye Fura‐2 in isolated, perfused rat TALs. Stretching cells increased Ca i by 243 ± 51 nM in SS TALs ( n =9; p <0.0008 vs. no stretch conditions) and by 124 ± 27 nM in SR TALs ( n =10; p <0.0005 vs no stretch conditions). The rise in Ca i caused by increasing cellular stretch was significantly higher in the SS group ( p <0.05 vs SR). When these animals were fed a high‐salt diet (4% NaCl) similar responses were obtained. Cellular stretch increased Ca i by 236 ± 58 nM in SS TALs ( n =7; p <0.004 vs no stretch conditions) and by 92 ± 15 nM in SR TALs ( n =6; p <0.0008 vs no stretch conditions). We have previously reported that the mechanosensitive Transient Receptor Potential Vanilloid 4 (TRPV4) is responsible for flow‐induced increases in Ca i . Thus we next tested whether TRPV4 expression was different between strains. TRPV4 was similarly expressed in TALs lysates from SS and SR that were fed either a control standard or a high‐salt diet. We conclude that SS TALs are more sensitive to increases in cellular stretch than SR TALs and that the difference is not due to TRPV4 expression.