Preferential renal tubular injury and increased renal sympathetic activity occur during the early stages of DOCA-salt hypertension in male rats.

Although renal dysfunction is present in arterial hypertension, the mechanisms underlying renal glomerular and tubular alterations remain incompletely understood. We investigated kidney changes during the progression of DOCA-salt hypertension, on renal sympathetic nerve activity (rSNA), its baroreceptor control, and markers of kidney function. Male Charles River rats were divided into independent experimental groups: controls (UNx), hypertensive (DOCA) rats treated for 3 and 5 weeks. All the animals underwent nephrectomy. Mean arterial pressure (MAP) and heart rate (HR) in awake rats, and rSNA and its baroreflex in anesthetized rats. Urinary biomarkers, total protein, gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), epidermal growth factor (EGF), cystatin C, β2-microglobulin (β2M), alpha-1 acid glycoprotein (AGP), neutrophil gelatinase-associated lipocalin (NGAL), and albumin and renal morphology were evaluated. Baseline rSNA was elevated after 3 weeks of treatment and remained increased at 5 weeks, associated with an increase in MAP and reduced baroreflex sensitivity. Urinary LDH and GGT markers were higher in hypertensives, with GGT remaining elevated. AGP, NGAL, and albumin levels were unchanged. EGF, β2M, and particularly cystatin C were significantly elevated in 3 and 5 weeks. These findings indicate that preferential renal tubular injury associated with increased rSNA occurs during the early stage of DOCA-salt hypertension.