Insulin resistance is the main target in preventing accelerating arterial aging

I.S. Strazhesko, O.N. Tkacheva, D.U. Akasheva, A.S. Kruglikova, E.V. Plokhova, O.U. Isaykina, M.S. Poktovskaya, V.A. Vygodin, V.S. Pykhtina, S.A. Boytsov
2013 Artery Research  
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
more » ... rtery 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 (16.1AE1.1 vs. 23.2AE1.0%), 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 (30AE10 vs. -16AE8 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.
doi:10.1016/j.artres.2013.10.127 fatcat:qhrfiru2x5d4xiebr27hx35gcu