PROSTAGLANDIN E(2) REGULATION OF ION-TRANSPORT IS ABSENT IN MEDULLARYTHICK ASCENDING LIMBS FROM SHR

Regulation of HCO3- and Cl- absorption by arginine vasopressin (AVP) a nd prostaglandin E(2) (PGE(2)) was examined in isolated, perfused medu llary thick ascending limbs (MTAL) from 4- to 7-wk-old spontaneously h ypertensive (SHR) and Wistar-Kyoto (WKY) rats. AVP inhibited HCO3- abs orption by 50% at 10(-10) M and by 25% at 2 x 10(-12) M in MTAL from b oth WKY and SHR. Cholera toxin (10(-9) M) or forskolin (10(-6) M) in t he bath also inhibited HCO3- absorption by 50% in the SHR. In MTAL fro m WKY, PGE(2) (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 decr eased 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 condition s, PGE(2) had no effect on HCO3- or Cl- absorption in MTAL from SHR. P GE(2) also reversed submaximal inhibition of HCO3- absorption by 2 x 1 0(-12) M AVP in WKY but not in SHR. With 10(-10) M AVP in the bath, ph orbol 12-myristate 13-acetate (10(-6) M in the bath) increased HCO3- a bsorption from 6.6 +/- 0.5 to 12.3 +/- 0.4 pmol . min(-1). mm(-1) in M TAL 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 HCO3- absorption and inhibit Cl- absorp tion 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 HCO3- absorption by AVP via adenosine 3',5'-cyclic m onophosphate is similar in MTAL from WKY and SHR. The lack of PGE(2) i nhibition of NaCl absorption in the MTAL may contribute to renal salt retention during the development of hypertension in the SHR.