Effect of an acute and chronic slat load on microvascular permeability in healthy subjects.
Abstract
Objective:
Abnormal microvascular structure and function have been related to hypertension. Increasing evidence links Na+ to microvascular changes. Whether a chronic dietary Na+ load or an acute IV Na+ load differs in its microvascular effects is unknown. We therefore studied both effects in normotensive subjects on the microcirculation.
Design and method:
Twelve healthy male subjects pursued a low-sodium diet (LSD,<50 mmol Na+/d) and a high-sodium diet(HSD,>200 mmol Na+/d) for 8 days in randomized order, separated by a crossover period. On day 8 of LSD hypertonic IV saline (5mmol Na+/L body water) was administered in 30 minutes. Microvascular permeability after both diets and after IV saline was determined with transcapillary escape rate of 125I-albumin(TERalb) after IV administration of 100kBq 125I-albumin. Blood samples were drawn at fixed time points until 60 min. Plasma radioactivity was measured with an automatic γ-counter. TERalb was expressed as percentage decline in plasma radioactivity per hour (%cpm/g/h) using regression analysis. Plasma volume was determined by calculating the y-intercept of the TERalb disappearance curve, corrected for injected dose of tracer. Sublingual Sidestream Darkfield imaging was performed to assess perfused boundary region (PBR), reflecting endothelial glycocalyx thickness, and RBC filling and microvascular density as measures of microvascular perfusion (Glycocheck software). Blood pressure (BP), heart rate (HR), cardiac output (CO) and systemic vascular resistance (SVR) were measured in supine position with Nexfin.
Results:
An overview of results is presented in the table. All subjects adhered to both diets. Body weight increased significantly after HSD. TERalb and plasma volume did not differ between LSD and HSD, but increased significantly after saline infusion. PBR showed no differences between LSD and HSD, or after saline infusion. RBC filling and microvascular density did not differ between diets or after saline infusion. BP, HR, CO and SVR were similar after all conditions.
Conclusions:
Acute, but not chronic Na+ loading in healthy subjects resulted in higher microvascular permeability that coincided with increased plasma volume. These results suggest that deleterious microvascular effects of an acute Na+ load may develop by hydrostatic, or hypertonic, or direct effects of Na+ to the endothelium.