Artery Research

Volume 7, Issue 3-4, September 2013, Pages 136 - 137

P4.05 POLYCYSTIN DEFICIENCY RESULTS IN COMPLETE LOSS OF NO SYNTHESIS DURING SUSTAINED FLOW-MEDIATED DILATATION OF CONDUIT ARTERIES IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: POSSIBLE REVERSAL BY DOPAMINE

Authors
A. Lorthioir1, R. Joannidès2, 3, I. Rémy-Jouet3, C. Fréguin-Bouilland1, M. Iacob2, C. Monteil4, D. Lucas5, M.P. Audrezet5, D. Guerrot1, 3, V. Richard2, 3, C. Thuillez2, 3, M. Godin1, 3, J. Bellien2, 3
1Department of Nephrology - Rouen University Hospital, Rouen, France
2Department of Pharmacology - Rouen University Hospital, Rouen, France
3INSERM U1096 - University of Rouen, Rouen, France
4EA 4651 - University of Rouen, Rouen, France
5INSERM U613 - University of Brest, Brest, France
Available Online 11 November 2013.
DOI
10.1016/j.artres.2013.10.124How to use a DOI?
Abstract

Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is due to mutations in genes PKD1 and PKD2 encoding polycystin-1 and -2, which transduce flow variations into cellular signals in the renal epithelium but also in vascular endothelium. However, the impact of polycystin deficiency on the release of endothelium-derived factors during flow variations is unknown.

Methods: In 21 normotensive ADPKD patients with normal kidney function and 21 control subjects, radial artery diameter and blood flow were measured during hand skin heating and post-ischemic hyperaemia. Local blood samples were drawn during heating to quantify plasma nitrite, indicator of nitric oxide (NO) availability, epoxyeicosatrienoic acids (EETs) and endothelin-1.

Results: Basal inflammatory and oxidative stress markers were similar between groups. Flow-mediated dilatation was lower in ADPKD patients than in controls during heating (16.1±1.1 vs. 23.2±1.0%), as confirmed by their downward shift of the diameter-shear stress relationship, but not during post-ischemic hypaeremia, and without difference in endothelium-independent dilatation to glyceryl trinitrate. Nitrite increased during heating in controls but not in patients (30±10 vs. −16±8 nmol/L). Plasma EETs tended to increase in controls but not in patients, without difference in endothelin-1 reduction. Intra-brachial infusion of dopamine (0.25–0.5 mg/kg/min) during heating induced a dose-dependent upward shift of the diameter-shear stress relationship in ADPKD patients and restoration of NO release.

Conclusions: ADPKD patients display a loss of NO release and subsequent reduction in endothelium-dependent dilatation during sustained flow increase. The prevention of this alteration by dopamine may help to reduce the high prevalence of cardiovascular diseases in ADPKD.

Open Access
This is an open access article distributed under the CC BY-NC license.

Journal
Artery Research
Volume-Issue
7 - 3-4
Pages
136 - 137
Publication Date
2013/11/11
ISSN (Online)
1876-4401
ISSN (Print)
1872-9312
DOI
10.1016/j.artres.2013.10.124How to use a DOI?
Open Access
This is an open access article distributed under the CC BY-NC license.

Cite this article

TY  - JOUR
AU  - A. Lorthioir
AU  - R. Joannidès
AU  - I. Rémy-Jouet
AU  - C. Fréguin-Bouilland
AU  - M. Iacob
AU  - C. Monteil
AU  - D. Lucas
AU  - M.P. Audrezet
AU  - D. Guerrot
AU  - V. Richard
AU  - C. Thuillez
AU  - M. Godin
AU  - J. Bellien
PY  - 2013
DA  - 2013/11/11
TI  - P4.05 POLYCYSTIN DEFICIENCY RESULTS IN COMPLETE LOSS OF NO SYNTHESIS DURING SUSTAINED FLOW-MEDIATED DILATATION OF CONDUIT ARTERIES IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: POSSIBLE REVERSAL BY DOPAMINE
JO  - Artery Research
SP  - 136
EP  - 137
VL  - 7
IS  - 3-4
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2013.10.124
DO  - 10.1016/j.artres.2013.10.124
ID  - Lorthioir2013
ER  -