Introduction: This study examined the association of losartan induced changes in urinary
metabolomic profile with the changes in blood pressure (BP) and renin-angiotensinaldosterone system (RAAS) in spontaneously hypertensive rats (SHR). Methods: Male SHR
were administered with either 0.5 mL of distilled water (control group, n=6) or 10 mg.kg-1 of
losartan (group 2, n=6) daily by oral gavage for 4 weeks. Body weight, BP, food and water
intake were measured weekly. At week 4, urine was collected for urinary electrolyte analysis
and metabolite profiling, after which the animals were euthanised by decapitation and blood
was collected for analysis of components of RAAS and electrolyte concentrations. Urine
metabolite profile of SHR was determined using proton nuclear magnetic resonance (
1H-NMR)
spectrometry combined with multivariate data analysis. Results: At week 4, losartan-treated
SHR had significantly lower BP than non-treated SHR. There were no differences in water
and food intake, body weight, serum and urinary electrolyte concentrations or in their urinary
excretions between the two groups. No differences were evident in the components of RAAS
except that the angiotensinogen level was significantly higher in losartan-treated SHR
compared to non-treated SHR. Orthogonal partial least squares discriminant analysis (OPLSDA) showed clear separation of urinary metabolites between control and losartan-treated
SHR. Losartan-treated SHR group was separated from the control group by changes in the
intermediates involved in glycine, serine and threonine metabolism. Conclusion:
Antihypertensive effect of losartan in SHR seems to be associated with changes in urinary
metabolite profile, particularly involving the metabolism of glycine, serine and threonine.