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
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- 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.
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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 -