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

Regulation of HCO 3 - and Cl - absorption by arginine vasopressin (AVP) and prostaglandin E 2 (PGE 2 ) 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 HCO 3 - 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 HCO 3 - absorption by 50% in the SHR. In MTAL from WKY, PGE 2 (10 -6 M in the bath) increased HCO 3 - 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, PGE 2 had no effect on HCO 3 - or Cl - absorption in MTAL from SHR. PGE 2 also reversed submaximal inhibition of HCO 3 - absorption by 2 x 10 -12 M AVP 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 HCO 3 - 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 PGE 2 to stimulate HCO 3 - absorption and inhibit Cl - absorption in the presence of AVP are absent in MTAL from SHR, 2) the defect may involve an inability of PGE 2 to stimulate protein kinase C, and 3) regulation of HCO 3 - absorption by AVP via adenosine 3',5'-cyclic monophosphate is similar in MTAL from WKY and SHR. The lack of PGE 2 inhibition of NaCl absorption in the MTAL may contribute to renal salt retention during the development of hypertension in the SHR.