Prostaglandin e2 regulation of ion transport is absent in medullary
thick ascending limbs from spontaneously hypertensive rats.
Good, David W., Carlton R. Caflisch, and Thampi George.
Departments of Medicine and Physiology & Biophysics, University of
Texas Medical Branch, Galveston, Texas 77555-0562
APStracts 2:0021F, 1995.
Regulation of HCO and Cl- absorption by vasopressin (AVP) and
prostaglandin E2 (PGE2) was examined in isolated, perfused medullary
thick ascending limbs (MTAL) from 4 - 7 week old spontaneously
hypertensive (SHR) and Wystar-Kyoto (WKY) rats. AVP inhibited HCO
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 (10-9M) or forskolin (10-6 M) in the
bath also inhibited HCO absorption by 50% in the SHR. In MTAL from
WKY, PGE2 (10-6M in the bath) increased HCO absorption from 7.1 +/- 0.4
to 12.0 +/- 0.4 pmol/min/mm (P<0.005) and decreased Cl- absorption from
65 +/- 7 to 47 +/- 6 pmol/min/mm (P<0.001) in the presence of 10-10 M
AVP. Under the same conditions, PGE2 had no effect on HCO or Cl-
absorption in MTAL from SHR. PGE2 also reversed submaximal inhibition
of HCO absorption by 2 x 10-12 M AVP in WKY but not in SHR. With 10-10
M AVP in the bath, phorbol myristate acetate (10-6 M in the bath)
increased HCO absorption from 6.6 +/- 0.5 to 12.3 +/- 0.4 pmol/min/mm in
MTAL from WKY and from 7.6 +/- 0.7 to 12.6 +/- 1.2 pmol/min/mm in SHR
(P<0.005). These results demonstrate that: 1) the effects of PGE2 to
stimulate HCO 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
HCO absorption by AVP via cyclic AMP 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.
Received 10 November 1994; accepted in final form 13 February
1995.
APS Manuscript Number F405-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 February 1995.