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

• Main Authors: A. Lorthioir, R. Joannidès, I. Rémy-Jouet, C. Fréguin-Bouilland, M. Iacob, C. Monteil, D. Lucas, M.P. Audrezet, D. Guerrot, V. Richard, C. Thuillez, M. Godin, J. Bellien
• Format: Article
• Language: English
• Published: Atlantis Press 2013-11-01
• Series: Artery Research
• Online Access: https://www.atlantis-press.com/article/125939021/view

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.