#2577 Sodium-mediated blood pressure rise is associated with a lower vasodilation response to nitroglycerin in healthy controls, but not in CKD

Abstract Background and Aims Chronic kidney disease (CKD) is characterized by endothelial dysfunction, that is partly caused by reduced bioavailability of NO. In addition to volume overload, endothelial dysfunction may contribute to hypertension in CKD. High sodium consumption affects NO levels, potentially leading to impaired vasorelaxation and a salt-sensitive blood pressure (BP) response. Whether salt-sensitivity in CKD is related to impaired NO bioavailability remains unknown. In this randomized-crossover-study, the vasoresponse to the NO donor nitroglycerin (NTG) during a high sodium diet in both CKD and healthy controls (HC) was assessed. Method CKD-patients (KDIGO stage G2-3A, proteinuria 0.5 g/d) and HC followed a 7-day low sodium control diet (50 mmol/d) and high sodium diet (200 mmol/d) in random order. After each diet, the hemodynamic profile was assessed by daytime BP and cardiac output (CO) measurements, by which systemic vascular resistance (SVR) was calculated. Nitroglycerin was administered to assess SVR changes. Results We included 15 CKD-patients (mean age, 49 yrs; median (IQR) proteinuria 0.7 (0.6-1.4) g/d; and plasma creatinine 129 (105-160) µmol/l) and 16 HC (41 yrs). Dietary salt intervention was comparable in the CKD and HC groups. After HSD, mean (SD) systolic BP increased in CKD by 9.7 mmHg (9.8; p 0.01) as compared to 3.1 mmHg ((6.0), p = 0.07)) in HC (between-group difference p = 0.04). After HSD, changes in body weight and CO did not differ between groups. Median (IQR) SVR change after HSD was 163.0 (−34.9-275.7) in CKD and −13.8 ((−299.4–61.4),p = 0.03) dyn⋅sec⋅cm-5 in HC. In HC, salt-mediated blood pressure change was positively associated with a NTG-induced SVR change during HSD (r = 0.70, p = 0.01). This association was not present in CKD (r = −0.24, p = 0.34) and significantly different from that in HC (p 0.01). Conclusion CKD-patients have a higher sodium-mediated BP response with comparable change of fluid status but a different SVR change as compared to HC. In HC, impaired sensitivity to the NO donor nitro-glycerin associates with higher BP response to sodium. No such association was found in CKD-patients, suggesting that persistent endothelial dysfunction is pivotal for salt sensitivity in CKD.