High salt intake increases blood pressure in normal rats: putative role of 20-HETE and no evidence on changes in renal vascular reactivity

Abstract

Background/Aims . High salt (HS) intake may elevate blood pressure (BP), also in animals without genetic salt sensitivity. The development of salt-dependent hypertension could be mediated by endogenous vasoactive agents; here we examined the role of vasodilator epoxyeicosatrienoic acids (EETs) and vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE).

Methods: In conscious Wistar rats on HS diet systolic BP (SBP) was examined after chronic elevation of EETs using 4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (c-AUCB), a blocker of soluble epoxide hydrolase, or after inhibition of 20-HETE with 1-aminobenzotriazole (ABT). Thereafter, in acute experiments the responses of renal artery blood flow (Transonic probe) and renal regional perfusion (laser-Doppler) to intrarenal acetylcholine (ACh) or norepinephrine were determined.

Results: HS diet increased urinary 20-HETE excretion. The SBP increase was not reduced by c-AUCB but prevented by ABT until day 5 of HS exposure. Renal vasomotor responses to ACh or norepinephrine were similar on standard and HS diet. ABT but not c-AUCB abolished the responses to ACh. Conclusions . 20-HETE seems to mediate the early-phase HS diet-induced BP increase while EETs are not engaged in the process. Since HS exposure did not alter renal vasodilator responses to Ach, endothelial dysfunction is not a critical factor in the mechanism of salt-induced blood pressure elevation.

Fig. 1

Systolic blood pressure (SBP, tail cuff method) in conscious rats maintained on standard (STD) or high (HS) sodium diet, untreated or pretreated with ABT (1-aminobenzotriazole) or c-AUCB (cis-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid. Means ± SEM, * significantly different from day 0, † significantly different from STD, # significantly different from HS; p<0.05.

Fig. 2

Changes in total renal blood flow (RBF) and flows through the cortex (CBF) and outer (OMBF) and inner medulla (IMBF) in response to acetylcholine and norepinephrine infused into renal artery. The data for day 10 of exposure to diets. Means ± SEM, * significantly different from pre-infusion control, † significantly different from standard diet.

Fig. 3

Changes in total renal blood flow (RBF) and flows through the cortex (CBF) and outer (OMBF) and inner medulla (IMBF) in response to acetylcholine (5 or 10 μg/kg/h) and norepinephrine (10 or 30 μg/kg/h) infused into renal artery. HS - high sodium diet, ABT-1-aminobenzotriazole), c-AUCB - cis-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid. The data for day 10 of exposure to diets. Means ± SEM, * significantly different from pre-infusion control, † significantly different from untreated HS rats.

Fig. 4

Effects of high sodium diet (HS) and/or inhibition of CYP-450 dependent monooxygenases (ABT) on mean arterial blood pressure (MABP), medullary blood flow (MBF) and medullary tissue nitric oxide (NO) signal. The data for day 21 of exposure to diet. Means ± SEM, * significantly different from untreated STD rats, # significantly different from untreated rats on the same diet. (p<0.05, n=5–9).