Prostaglandin E₂ regulation of ion transport is absent in medullary thick ascending limbs from SHR

Regulation of HCO₃/^- and Cl^- absorption by arginine vasopressin (AVP) and prostaglandin E₂ (PGE₂) was examined in isolated, perfused medullary thick ascending limbs (MTAL) from 4- to 7-wk-old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. AVP inhibited HCO₃/^- absorption by 50% at 10^-10 M and by 25% at 2 x 10^-12 M in MTAL from both WKY and SHR. Cholera toxin (10^-9 M) or forskolin (10^-6 M) in the bath also inhibited HCO₃/^- absorption by 50% in the SHR. In MTAL from WKY, PGE₂ (10^-6 M in the bath) increased HCO₃/^- absorption from 7.1 ± 0.4 to 12.0 ± 0.4 pmol · min^-1 · mm^-1 (p < 0.005) and decreased Cl^- absorption from 65 ± 7 to 47 ± 6 pmol · min^-1 · mm^-1 (P < 0.001) in the presence of 10^-10 M AVP. Under the same conditions, PGE₂ had no effect on HCO₃/^- or Cl^- absorption in MTAL from SHR. PGE₂ also reversed submaximal inhibition of HCO₃/^- absorption by 2 x 10^-12 MAVP in WKY but not in SHR. With 10^{- 10} M AVP in the bath, phorbol 12-myristate 13-acetate (10^-6 M in the bath) increased HCO₃/^- absorption from 6.6 ± 0.5 to 12.3 ± 0.4 pmol · min^-1 · mm^-1 in MTAL from WKY and from 7.6 ± 0.7 to 12.6 ± 1.2 pmol · min^-1 · mm^-1 in MTAL from SHR (P < 0.005). These results demonstrate that 1) the effects of PGE₂ to stimulate HCO₃/^- absorption and inhibit Cl^- absorption in the presence of AVP are absent in MTAL from SHR, 2) the defect may involve an inability of PGE₂ to stimulate protein kinase C, and 3) regulation of HCO₃/^- absorption by AVP via adenosine 3',5'-cyclic monophosphate is similar in MTAL from WKY and SHR. The lack of PGE₂ inhibition of NaCl absorption in the MTAL may contribute to renal salt retention during the development of hypertension in the SHR.