Nitric oxide inhibits adh-stimulated osmotic water permeability in
cortical collecting ducts..
Garc[acute]ia, N[acute]estor H., Silvia I. Pomposiello, and Jeffrey L.
Garvin.
Division of Hypertension and Vascular Research, Henry Ford
Hospital, 2799 West Grand Blvd., Detroit, 48202 MI
APStracts 2:0143F, 1995.
Nitric oxide (NO) reduces blood pressure in vivo by two mechanisms,
vasodilation and increasing urinary volume; however, the exact
mechanism by which it increases urinary volume is not clear. We
hypothesized that NO inhibits antidiuretic hormone (ADH)-stimulated
fluid reabsorption (Jv) by the isolated rat cortical collecting duct
(CCD) by decreasing water permeability (Pf) and sodium reabsorption
(JNa). In the presence of 10-11M ADH, Jv was 0.15 +/- 0.04 nl/min.mm;
after 10-6M spermine NONOate (SPM) was added to the bath, Jv
decreased to 0.06 +/- 0.03 nl/min.mm (p < 0.03). To investigate
whether the inhibition of Jv was the result of decreased Pf and/or
JNa, we first tested the effect of SPM on ADH-stimulated Pf. Basal Pf
was stimulated to 289.2 +/- 77.3 [mu]m/sec after 10-11M ADH was added
to the bath (p < 0.01). SPM decreased Pf to 159.8 +/- 45.0
_m/sec (p < 0.05). To ensure that this effect on Pf was due to
NO release, we used another NO donor, nitroglycerin (NTG). Pf was
initially -25.8 +/- 18.3 [mu]m/sec and increased to 133.9 +/- 30.5
[mu]m/sec after addition of 10-11M ADH (p < 0.002). 20 [mu]M NTG
lowered Pf to 92.4 +/- 18.4 [mu]m/sec (p < 0.02). In the
presence of 10-9M ADH, NTG also decreased Pf (p < 0.04). Next we
investigated the effect of SPM on ADH-stimulated JNa. In the presence
of ADH, JNa was 37.8 +/- 7.3 pmol/min.mm. After SPM was added, it
dropped to 24.3 +/- 5.1 pmol/min.mm (p < 0.05). Time controls
exhibited no change in ADH-stimulated Jv, Pf or JNa. We concluded
that 1) NO decreases ADH-stimulated water and sodium transport in the
isolated CCD, and 2) water reabsorption is inhibited by a primary
effect on Pf. A direct effect of NO on the CCD may explain its
natriuretic and diuretic effects observed in vivo.
Received 23 September 1995; accepted in final form 31 July 1995.
APS Manuscript Number F64-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.