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Effect of Gene Variants on Dopamine Receptor Natriuretic Responses

NCT00592150 · Status: UNKNOWN · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 44

Last updated 2013-01-23

No results posted yet for this study

Summary

Hypothesis to be tested: Dopamine D1-like receptor-induced natriuresis is impaired in humans with G protein-related kinase 4 gene variants.

Our research group has discovered a D1 receptor/adenylyl cyclase coupling defect in renal PTCs from subjects with essential hypertension. We have found increased GRK-4 activity in renal PTCs in human essential hypertension due to activating variants of GRK-4, an effect that was reproduced in a transfected cell model. Preventing the translation of GRK-4 normalized the coupling of the D1 receptor to adenylyl cyclase in hypertension. Gene variants of GRK-4 cause a ligand-independent serine-phosphorylation of the D1 receptor, resulting in its uncoupling from the G-protein/effector complex. The desensitization of the D1 receptor in the renal PTC is hypothesized to be the cause of the compromised natriuretic effect of DA that eventually leads to Na+ retention and hypertension. The primary objective of this protocol is to demonstrate that natriuresis engendered by D1-like receptor activation with fenoldopam is blunted in subjects with 3 or more SNPs of GRK-4 compared with responses in subjects with 0-2 SNPs.

Conditions

Interventions

DRUG

fenoldopam

The fenoldopam infusion rate will be 0.05 μg/kg/min for 3 hours

DRUG

Placebo

Placebo infusion for 3 hours

Sponsors & Collaborators

  • National Institutes of Health (NIH)

    collaborator NIH

  • University of Virginia

    lead OTHER

Principal Investigators

  • Robert M Carey, MD · University of Virginia

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Model
CROSSOVER

Eligibility

Min Age
18 Years
Max Age
70 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2007-06-30
Primary Completion
2008-03-31
Completion
2013-06-30

Countries

  • United States

Study Locations

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Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00592150 on ClinicalTrials.gov