title: Nitric oxide inhibits ADH-stimulated osmotic water permeability in cortical collecting ducts.
abstract: 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 (J(r)) by the isolated rat cortical collecting duct (CCD) by decreasing water permeability (Pf) and sodium reabsorption (Jna). In the presence of 10(-11) MADH, Jv was 0.15 +/- 0.04 nl.min-1.mm-1; after 10(-6) M spermine nonoate (SPM) was added to the bath. Jv decreased to 0.06 +/- 0.03 nl.min-1.mm-1 (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 microns/s after 10(-11) M ADH was added to the bath (P < 0.01). SPM decreased Pf to 159.8 +/- 45.0 microns/s (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 microns/s and increased to 133.9 +/- 30.5 microns/s after addition of 10(-11) M ADH (P < 0.002). NTG, 20 microM, lowered Pf to 92.4 +/- 18.4 microns/s (P < 0.02). In the presence of 10(-9) M 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-1.mm-1. After SPM was added, it dropped to 24.3 +/- 5.1 pmol.min-1.mm-1 (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 isolate 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.
authors.affiliation: Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, Michigan 48202, USA.
authors.forename: N H
authors.initials: NH
authors.lastname: García
authors.forename: S I
authors.initials: SI
authors.lastname: Pomposiello
authors.forename: J L
authors.initials: JL
authors.lastname: Garvin
mesh_terms: D000818:Animals; D004231:Diuresis / Q000502:physiology; D066298:In Vitro Techniques; D007672:Kidney Cortex; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009569:Nitric Oxide / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology; D009995:Osmosis / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014667:Vasopressins / Q000494:pharmacology*; D014867:Water / Q000378:metabolism*
chemical_list: D014867:Water; D014667:Vasopressins; D009569:Nitric Oxide; D005996:Nitroglycerin