Document Detail


Differential human renal tubular responses to dopamine type 1 receptor stimulation are determined by blood pressure status.
MedLine Citation:
PMID:  9039090     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We performed the present studies to determine whether a proximal renal tubular dopamine D1-like receptor defect exists in human essential hypertension. Twenty-four subjects were studied (13 normotensive and 11 hypertensive) in a randomized, double-blind, vehicle-controlled study using fenoldopam, a selective D1-like receptor agonist. Subjects were studied in sodium metabolic balance at 300 mEq/d, after which the salt sensitivity of their blood pressure was determined. Fenoldopam at peak doses of 0.1 to 0.2 microgram/kg per minute decreased mean arterial pressure in hypertensive subjects but did not change mean pressure in normotensive subjects. Fenoldopam increased renal plasma flow to a greater extent in hypertensive than normotensive subjects. Fenoldopam increased both urinary and fractional sodium excretions in the hypertensive and normotensive groups. In normotensive but not hypertensive subjects, fenoldopam increased the fractional excretion of lithium and distal sodium delivery. In contrast, both distal fractional sodium reabsorption and sodium-potassium exchange fell significantly in hypertensive subjects. We conclude that human essential hypertension is associated with a reduction in the proximal tubular response to D1-like receptor stimulation compared with normotensive subjects. Hypertensive subjects appear to have a compensatory upregulation of renal vascular and distal tubular D1-like receptor function that offsets the proximal tubular defect, resulting in an enhanced natriuretic response to D1-like receptor stimulation.
Authors:
D P O'Connell; N V Ragsdale; D G Boyd; R A Felder; R M Carey
Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Hypertension     Volume:  29     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-03-10     Completed Date:  1997-03-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  115-22     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Therapeutics, University College Cork, Ireland.
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MeSH Terms
Descriptor/Qualifier:
Adult
Blood Pressure / drug effects
Cross-Over Studies
Dopamine Agonists / administration & dosage,  pharmacology*
Double-Blind Method
Female
Fenoldopam / administration & dosage,  pharmacology*
Heart Rate / drug effects
Humans
Hypertension / etiology,  metabolism*,  physiopathology
Infusions, Intravenous
Inulin / diagnostic use,  pharmacokinetics
Kidney Tubules / drug effects*,  physiology
Lithium / urine
Male
Middle Aged
Natriuresis / drug effects
Receptors, Dopamine D1 / drug effects*,  metabolism
Renal Plasma Flow / drug effects
Sodium / urine
Sodium, Dietary / administration & dosage,  adverse effects
Grant Support
ID/Acronym/Agency:
M01-RR-800847/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Dopamine Agonists; 0/Receptors, Dopamine D1; 0/Sodium, Dietary; 67227-56-9/Fenoldopam; 7439-93-2/Lithium; 7440-23-5/Sodium; 9005-80-5/Inulin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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