The spontaneously hypertensive rats (SHR) is one of the major experimental models of hypertension. In this model, renaldamage is pressure-dependent and consists of arterial hypertrophy that leads to the collapse of some glomeruli, tubular atrophy and compensatory hyperfiltration in another population of glomeruli (Hultström, 2012). In previous works, we have demonstrated that urinary aminopeptidase activities can act as early biomarkers of renal dysfunction in cisplatin-treated rats (Quesada et al., 2012; Montoro-Molina et al., 2014). The aim of this work is to study the potential use of urinary aminopeptidase activities as biomarkers of renal dysfunction in SHR. 10 Wistar-Kyoto (WKY) rats and 10 SHR were housed from 8 to 32 weeks of age. Once a month, 24-h urine collection was made. Body weight, food and water intake, and systolic blood pressure (SBP) were also measured. Urine samples were centrifuged and supernatants were frozen at -80 °C. At the end of the experiment, blood samples were obtained from carotid artery under anaesthesia with pentobarbital (50 mg/kg i.p.), and animals were sacrificed with an overdose of pentobarbital (150 mg/kg, i.p.). In urine samples we measured dipeptidylpeptidase-IV (DPP4), glutamyl (Glu) and alanyl aminopeptidase (AlaAp) activities by fluorimetry. Proteinuria, urine and serum creatinine (SCr) were analyzed in a Spin120 autoanalyzer. All experimental procedures were performed according to the European Union Guidelines to the Care and Use of Laboratory Animals and approved by the Ethical Committee of the University of Jaén. Urinary AlaAP, GluAP and DPP4 activities (nmol/min/mg creatinine) were significantly increased in SHR at 8, 12, 16, 20, 24, 28 and 32 weeks. Proteinuria (mg/mg creatinine) was increased at 8, 12, 20, 24 and 32 weeks, decreased at 16 weeks and remained unchanged at 28 weeks. We found significant correlations (p<0.001) between aminopeptidase activities and SBP. Proteinuria did not correlate with SBP. At the end of the experiment, SCr (mg/dl) was decreased in SHR (0.36 ± 0.01) vs WKY (0.48 ± 0.02; p<0.001), and creatinine clearance (ml/min/g kidney) was higher in SHR (0.64 ± 0.05 vs 0.46 ± 0.02; p<0.01). These findings suggest that urinary aminopeptidase activities can be used to assess pressure-dependant renal damage in SHR. Besides, SCr concentration is decreased in SHR due to glomerular hyperfiltration. Therefore, these enzymes could have a potential application in the evaluation of chronic kidney diseases that could course with glomerular hyperfiltration, especially when SCr cannot be used as a marker of renal dysfunction.