Nitric Oxide–Induced Inhibition of Transport by Thick Ascending Limbs From Dahl Salt-Sensitive Rats

Abstract

Abstract —The factor responsible for salt sensitivity of blood pressure in Dahl rats is unclear but presumably resides in the kidney. We tested the hypotheses that (1) thick ascending limbs of Dahl salt-sensitive rats (DS) absorb more NaCl than those of Dahl salt-resistant rats (DR) and (2) NO inhibits transport to a lesser extent in thick ascending limbs from DS. We found that basal chloride absorption (J Cl ) by thick ascending limbs from DR was 105.8±10.0 pmol · mm −1 · min −1 (n=6). Ten and 100 μmol/L spermine NONOate, an NO donor, decreased J Cl in DR to 65.8±8.5 and 46.8±7.0 pmol · mm −1 · min −1 , respectively. Basal J Cl in DS was 131.6±13.4 pmol · mm −1 · min −1 (n=7). In DS, 10 and 100 μmol/L spermine NONOate decreased J Cl to 111.5±12.8 and 46.8±6.2 pmol · mm −1 · min −1 , respectively. No difference was observed in basal or NO-inhibited Na absorption by cortical collecting ducts or in basal or NO-inhibited oxygen consumption by inner medullary collecting ducts. Because NO acts via generation of cGMP, we measured cGMP production by thick ascending limbs from DS and DR to see whether a difference in cGMP production could account for the difference in basal or NO-inhibited transport. Basal rates of cGMP production were similar between the 2 strains. Although NO increased cGMP production by thick ascending limbs from both strains, no difference existed between DS and DR. We concluded that the reduced ability of NO to block transport in thick ascending limbs in DS may account for at least part of the salt sensitivity of blood pressure in this strain.