The Role of Vasopressin in Salt-Mediated Blood Pressure Response in Healthy Volunteers and Patients With Chronic Kidney Disease.

Objective: Plasma osmolality increases with high salt intake and promotes release of arginine vasopressin (AVP), which may increase blood pressure by vasoconstriction and release of adrenocorticotropic hormone. In turn, elevated blood pressure activates arterial baroreceptors, which may inhibit AVP secretion, mitigating its involvement hypertension development. Rat studies suggest impaired baroreceptor inhibition of AVP-producing cells to contribute to salt-sensitive hypertension. This randomized crossover intervention trial aimed to explore the role of vasopressin in salt-sensitive hypertension in humans. Design and method: Healthy controls (HC) and chronic kidney disease (CKD) patients all followed both a 7 day low sodium diet (LSD, 12 g NaCl/day) in a randomized order, with 2 weeks normal diet wash-out period in between. On day 8 of each diet, office mean arterial pressure (MAP), mean baroreceptor sensitivity (xBRS) and laboratory measurements were taken. Plasma copeptin was used as surrogate for AVP. Differences between LSD and HSD were tested within and between groups. Results: We included 26 HC (mean age 47 years, 50% male) and 45 CKD patients (mean age 55 years, 74% male). Both groups exhibited a significant increase in plasma sodium and osmolality after HSD, but the plasma sodium increase was significantly higher in CKD patients than in HC (respectively, 3.0±2.2, vs. 1.8±1.7 mmol/L, p=0.02). In CKD patients, HSD increased MAP and xBRS significantly (respectively, 7.2±9.2 mmHg, p=0.02; 1.2±3.7 ms/mmHg p=0.02), but not in HC. The HSD did not increase copeptin in both groups, despite higher plasma sodium concentrations (HC: -0.6±4.8, CKD: -0.9±4.8). Conclusions: In CKD patients, HSD raised MAP, xBRS, and plasma sodium without changing copeptin, implying baroreceptor-mediated AVP inhibition and suggesting that salt-sensitivity is a water-losing phenotype, particularly, but not solely, in CKD.