Abstract 52: Enhanced Phosphodiesterase 5 (PDE5) in Thick Ascending Limbs of Dahl Salt Sensitive Rats Blunts NO-induced Inhibition of Transport

In normal rats, NO inhibits thick ascending limb (TAL) NaCl reabsorption via cGMP. In Dahl Salt Sensitive (SS) rats NO fails to decrease TAL NaCl absorption. However, the mechanism for this defect is unknown. NO stimulates soluble guanylyl cyclase to produce cGMP. The intracellular concentrations of cGMP and its effect are limited by PDE5, a cGMP-specific phosphodiesterase. We hypothesize that enhanced PDE5 expression in SS TALs blunts the inhibitory effect of NO on transport by decreasing cGMP concentration. We isolated TALs from SS and Dahl Salt-Resistant (SR) rats fed normal salt and measured PDE5 expression by Western blot. PDE5 expression was 210±20% higher in SS TALs compared to SR ( p 2 ) consumption in TALs. In SR TALs, the NO donor spermine-NONOate (NO) decreased O 2 consumption by 7.9±2.3% (p2 consumption by 7.7±2.3% (pvs SR: 0.4±0.2 fmoles/μg, p