Restoration of urine concentrating ability and accumulation of
medullary osmolytes after chronic diuresis.
Sone, Masayoshi, Akihiro Ohno, Gerd J. Albrecht, Klaus Thurau, and
Franz-X. Beck.
Department of Medicine, Kidney Center, Tokyo Women's Medical
College, Tokyo 162, Japan, HNO-Klinik im Klinikum Gro[beta]hadern,
Universit[umlaut]at M[umlaut]unchen, 81377 Munich, Germany,
Physiologisches Institut, Universit[umlaut]at M[umlaut]unchen, 80336
Munich, Germany
APStracts 2:0056F, 1995.
Restoration of urine osmolality (Uosm) and medullary osmolyte contents
after chronic diuresis was studied in rats infused for 6 days with
furosemide and given subse quently the vasopressin analogue dDAVP
([deamino-cys1, D-Arg8]-vasopressin). Papillary tip intra- and
extracellular electrolyte concentrations were measured by electron
micro probe analysis, tissue contents of methylamines
(glycerophosphorylcholine, betaine), polyols (myo-inositol, sorbitol)
and several amino acids in different kidney zones by HPLC.
Administering dDAVP continuously after diuresis increased Uosm from
(means +/- SEM) 348 +/- 8 to 1265 +/- 127 after 1 day and 2485 +/-
186 mosmol/kg H2O after 3 days. The sum of all osmolytes at the
papillary tip rose from 309.2 +/- 28.9 to 690.9 +/- 105.8 and 1282.8
+/- 21.0 mmol/kg protein after days 1 and 3 respectively. While
interstitial tonicity (sum of Na, Cl and K concentrations) was
increased by 116 and 223% after 1 and 3 days dDAVP, intracellular
tonicity was similar in chronic diuresis and following 1 or 3 days
dDAVP. Coadministration of dDAVP with betaine, myo-inositol and
choline ("osmolyte treatment") did not accelerate the
restoration of Uosm, but caused significantly higher contents of
osmolytes (except myo-inositol) in inner medulla and/or papilla after
3 days. In a minority of animals restoration of Uosm and
reaccumulation of medullary osmolytes were impeded in both dDAVP- and
dDAVP/osmolyte-treated rats. These data indicate that, after chronic
diuresis, accumulation of organic osmolytes and restoration of Uosm
proceed in parallel. Capacity for transport and/or synthesis of
organic osmolytes, rather than their availability, appear to limit
reaccumulation on the 1st day of recovery. By he 3rd day delivery of
some osmolytes, or their precursors, may limit the restoration of
medullary osmolyte content. The failure of some rats to attain
sufficient concentrating ability within this time period may be
related to deficient reaccumulation of medullary osmolytes.
Received 21 November 1994; accepted in final form 10 April 1995.
APS Manuscript Number F412-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 April 1995.