Acute Intra-Arterial Administration of Cholesterol Causes Renal Vasoconstriction and Antinatriuresis in Rats

An increase in circulating cholesterol level concentration chronically induces vascular dysfunction and aggravates the condition of hypertension. However, the mechanistic role of cholesterol in the pathophysiological process of hypertension remains poorly understood. To examine the hypothesis that increased cholesterol influences renal hemodynamic and tubular function leading to sodium retention, we evaluated the renal responses to polyoxyethanyl-cholesteryl sebacate (PEG-Chol) as well as cholesterol sequestered with methyl-cyclodextrin (MCD-Chol) at a dose 8μg/min/100g of body weight infused directly into the left renal artery of anesthetized male Sprague-Dawley rats for 60 min. Total renal blood flow (RBF) was measured by a Transonic flow probe and regional (cortical, CBF and medullary, MBF) blood flow was measured by laser-Doppler needle flow probes. Glomerular filtration rate (GFR) was determined by inulin clearance. Observed renal responses to acute infusion of PEG-Chol (n = 6) and MCD-Chol (n = 6) were similar, therefore these data were combined. Compared to the control period, administration of cholesterol caused slight decreased of 10 ± 2 % in RBF (baseline, B 7.6 ± 0.3 mL/min/g), 8 ± 1 % in CBF (B 210 ± 11 perfusion unit; PU), 7 ± 2 % in MBF (B 67 ± 4 PU) and 5 ± 2 % in GFR (B 0.87 ± 0.03mL/min/g). Moreover, cholesterol infusion also caused marked reductions of 14 ± 2 % in urine flow (B 12.9 ± 0.9 μL/min/g), 28 ± 3 % in sodium excretion (B 1.10 ± 0.08 μmol/min/g) and 22 ± 2 % in fractional sodium excretion (B 0.87 ± 0.06 %) without affecting potassium excretion. Infusion of vehicle did not cause any changes in renal parameters. These data suggest that hypercholesterolemia compromises the kidney's ability to excrete sodium appropriately and thus could play a role in the pathophysiology of salt-sensitivity and hypertension.