Skip to main page content

COVID-19 is an emerging, rapidly evolving situation.

Get the latest public health information from CDC: https://www.coronavirus.gov.
Get the latest research from NIH: https://www.nih.gov/coronavirus.
Find NCBI SARS-CoV-2 literature, sequence, and clinical content:
https://www.ncbi.nlm.nih.gov/sars-cov-2/.

National Institutes of Health

National Library of Medicine
National Center for Biotechnology Information
NCBI homepage
Log in

Access keys
NCBI Homepage
MyNCBI Homepage
Main Content
Main Navigation
Search:

Advanced
User Guide

Full text links

full-text provider logo
Actions
Favorites
Share

Page navigation

Title & authors

Abstract
Similar articles
Cited by
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources

Clinical Trial
J Am Soc Nephrol

. 1999 Oct;10(10):2165-70.
Selective V2-receptor vasopressin antagonism decreases urinary aquaporin-2
excretion in patients with chronic heart failure
P Y Martin 1 , W T Abraham, X Lieming, B R Olson, R M Oren, M Ohara, R W Schrier
Affiliations

PMID: 10505693

Free article
Abstract

Aquaporin-2 (AQP-2), a water channel located on the apical membrane of collecting

duct cells, regulates water reabsorption under the control of vasopressin (AVP).
Using an antibody directed to human AQP-2, a quantitative Western blot analysis was
performed to determine the collecting duct responsiveness to an oral, nonpeptide,
V2 receptor antagonist (VPA-985) in patients with chronic NYHA II and III heart
failure. Standards were derived by conjugating the immunizing peptide to maleimide-
activated bovine serum albumin and a standard curve was generated for each blot.
Quantification of baseline steady-state AQP-2 excretion was done by collecting
urine on the day before study drug administration. The next day patients received
either placebo or VPA-985 at one of four different doses and urine was collected
every 2 h. Thereafter, urinary AQP-2 excretion was calculated as a ratio of the
urine flow and was expressed in pmol/h. During baseline, steady-state excretion did
not change significantly (T0-T2, 458 +/- 44; T2-T4, 443 +/- 35; T4-T6, 422 +/- 35;
T6-T8, 401 +/- 30). Compared to placebo, urinary AQP-2 excretion decreased
significantly and in all groups in a dose-dependent manner during VPA-985
administration. The most impressive decrease was observed in the 250-mg group (T0-
T2, 89 +/- 5; T2-T4, 50 +/- 18; T4-T6, 43 +/- 22; T6-T8, 42 +/- 23; P < 0.001
during each period compared with baseline and placebo results). VPA-985
significantly increased solute-free water clearance and urine output and
significantly decreased urinary osmolality. Urinary AQP-2 excretion correlated best
with solute-free water clearance during T0-T2 and T2-T4 collection, but a
correlation with urinary osmolality and urinary output was also found during these
periods. In conclusion, AQP-2 urinary excretion, as measured by quantitative
Western analysis, is a sensitive biologic marker to assess the short-term
responsiveness of the collecting duct to a V2 receptor AVP antagonist in chronic
heart failure.
Similar articles

Urinary excretion of aquaporin-2 in humans: a potential marker of collecting

duct responsiveness to vasopressin.
Elliot S, Goldsmith P, Knepper M, Haughey M, Olson B. J Am Soc Nephrol. 1996
Mar;7(3):403-9. PMID: 8704105
Urinary excretion of aquaporin-2 in pathological states of water metabolism.
Ishikawa S. Ann Med. 2000 Mar;32(2):90-3. doi: 10.3109/07853890009011757. PMID:
10766399 Review.
[Urinary excretion of aquaporin-2 in water metabolism disorders].
Ishikawa S, Saito T, Saito T. Rinsho Byori. 1999 May;47(5):402-7. PMID:
10375960 Review. Japanese.
Aquaretic effect of lixivaptan, an oral, non-peptide, selective V2 receptor
vasopressin antagonist, in New York Heart Association functional class II and III
chronic heart failure patients.
Abraham WT, Shamshirsaz AA, McFann K, Oren RM, Schrier RW. J Am Coll Cardiol.
2006 Apr 18;47(8):1615-21. doi: 10.1016/j.jacc.2005.11.071. Epub 2006 Mar 29. PMID:
16630999 Clinical Trial.
Pharmacodynamic effects of a nonpeptide antidiuretic hormone V2 antagonist in
cirrhotic patients with ascites.
Guyader D, Patat A, Ellis-Grosse EJ, Orczyk GP. Hepatology. 2002
Nov;36(5):1197-205. doi: 10.1053/jhep.2002.36375. PMID: 12395330 Clinical Trial.

See all similar articles

Cited by 19 articles

Bortezomib as a probable cause of the syndrome of inappropriate antidiuretic

hormone secretion: A case report and review of the literature.
Lv CL, Li J. Mol Clin Oncol. 2017 Oct;7(4):667-672. doi: 10.3892/mco.2017.1366.
Epub 2017 Aug 7. PMID: 28856001 Free PMC article.
The V2 receptor antagonist tolvaptan raises cytosolic calcium and prevents AQP2
trafficking and function: an in vitro and in vivo assessment.
Tamma G, Di Mise A, Ranieri M, Geller A, Tamma R, Zallone A, Valenti G. J Cell
Mol Med. 2017 Sep;21(9):1767-1780. doi: 10.1111/jcmm.13098. Epub 2017 Mar 21. PMID:
28326667 Free PMC article.
 Urine Aquaporin-2: A Promising Marker of Response to the Arginine Vasopressin
Type-2 Antagonist, Tolvaptan in Patients with Congestive Heart Failure.
Imamura T, Kinugawa K. Int J Mol Sci. 2016 Jan 14;17(1):105. doi:
10.3390/ijms17010105. PMID: 26784173 Free PMC article. Review.
Arginine vasopressin as a target in the treatment of acute heart failure.
Gilotra NA, Russell SD. World J Cardiol. 2014 Dec 26;6(12):1252-61. doi:
10.4330/wjc.v6.i12.1252. PMID: 25548615 Free PMC article. Review.
Osmotic homeostasis.
Danziger J, Zeidel ML. Clin J Am Soc Nephrol. 2015 May 7;10(5):852-62. doi:
10.2215/CJN.10741013. Epub 2014 Jul 30. PMID: 25078421 Free PMC article. Review.

See all "Cited by" articles

Publication types

Clinical Trial
Comparative Study
Randomized Controlled Trial

MeSH terms

Administration, Oral
Aged
Aquaporin 2
Aquaporin 6
Aquaporins / drug effects
Aquaporins / urine*
Arginine Vasopressin / antagonists & inhibitors*
Azepines / administration & dosage*
Benzamides / administration & dosage*
Biomarkers / urine
Blotting, Western
Dose-Response Relationship, Drug
Double-Blind Method
Female
Heart Failure / diagnosis
Heart Failure / drug therapy*
Heart Failure / urine
Humans
Male
Middle Aged
Pyrroles
Reference Values
Sensitivity and Specificity

Substances

AQP2 protein, human

Aquaporin 2
Aquaporin 6
Aquaporins
Azepines
Benzamides
Biomarkers
Pyrroles
Arginine Vasopressin
lixivaptan

Related information
 MedGen
PubChem Compound (MeSH Keyword)

LinkOut - more resources

Full Text Sources

HighWire
Other Literature Sources
The Lens - Patent Citations
Medical
MedlinePlus Health Information
Miscellaneous
NCI CPTAC Assay Portal

full-text provider logo

Connect

Twitter
Facebook
YouTube
LinkedIn
GitHub

Blog
Support Center

National Center for Biotechnology Information

8600 Rockville Pike Bethesda, MD 20894 USA

About us Contact us Policies FOIA

Popular

PubMed
PubMed Central
Bookshelf
PubChem
Gene
BLAST
Nucleotide
Protein
GEO

Resources

Literature
Health
Genomes
Genes
Proteins
Chemicals

Actions

Submit
Download
Learn
Develop
 Analyze
Research

NLM  |  NIH  |  HHS  |  USA.gov

Feedback