ALTERATION OF RENAL DOPAMINERGIC SYSTEM IN RATS FED WITH HIGH FAT DIET: A POSSIBLE MECHANISM PROMOTING ARTERIAL HYPERTENSION

Abstract

Objective: A chronic high fat diet (HFD) induces insulin resistance and enhances renal sodium reabsorption. The renal dopaminergic system (RDS) is a local natriuretic system involved in blood pressure regulation. We analyzed the effect of a HFD on the RDS and its impact on blood pressure regulation in rats. Design and method: Six weeks old male Sprague-Dawley rats were divided into two groups (n = 4–6), and studied for 4, 8 and 12 weeks. C (Control): standard diet (SD) and tap water to drink; HFD: 50% w/w bovine fat added to SD and tap water to drink. We determined: Systolic blood pressure (SBP); urine excretion of L-dopa and dopamine by HPLC (L-dopa/dopamine index was calculated); plasmatic, urinary biochemical, and kidney function parameters; and organic cation transporter N1, 2 and 3 (OCT-N1/2/3) protein expression in renal cortex tissue by western blot. Results: SBP (mmHg): HFD4: 134 ± 2 vs. C4: 120 ± 2; HFD8: 135 ± 2 vs. C8: 121 ± 2; HFD12: 147 ± 2 vs. C12 115 ± 3; p < 0.01. fractional sodium excretion (FENa, %): HFD4: 0.19 ± 0.03 vs. C4: 0.63 ± 0.04; HFD8: 0.18 ± 0.02 vs. C8: 0.49 ± 0.06; HFD12: 0.05 ± 0.02 vs. C12 0.35 ± 0.05; p < 0.01. urinary sodium excretion (UNa.V, mEq/24hs): HFD4: 0.53 ± 0.05 vs. C4: 2.09 ± 0.15; HFD8: 0.51 ± 0.07 vs. C8: 1.94 ± 0.11; HFD12: 0.16 ± 0.04 vs. C12: 0.97 ± 0.17, p < 0.01. Daily diuresis (ml/24hs): HFD4: 3.6 ± 0,7 vs. C4: 13.5 ± 1.3; HFD8: 3.5 ± 0.3 vs. C8: 16.4 ± 2.2; HFD12: 4.3 ± 0.7 vs. C12: 15.3 ± 1.6, p < 0,0001. L-dopa/dopamine index: HFD4: 3.6 ± 0.3 vs. C4: 1.1 ± 0.2, p < 0.005; HFD8: 3.7 ± 0.7 vs. C8: 1.1 ± 0.2, p < 0.05; HFD12: 4.8 ± 0.2 vs. C12: 2.0 ± 0.3, p < 0.01. A positive correlation between SBP vs the L-dopa/dopamine index: p < 0.001, r = 0.985, R2 = 0.97; and a negative correlation between UNa.V vs L-dopa/dopamine index: p < 0.001, r = -0.959, R2 = 0.92 were found. Expression of transporter OCT-N1/2/3 / GAPDH were: HFD8: 0.6 ± 0.1 vs. C8: 1.0 ± 0.2, p < 0.05. Conclusions: The reduction in natriuresis could be related to the decrease in dopamine excretion to the proximal convoluted tubular lumen caused by the reduced expression of OCT-N1/2/3 transporters, contributing to increase blood pressure.