Gliflozins (sodium-glucose transporter-2 inhibitors) exhibited renoprotective effects not only in diabetic but also in non-diabetic patients with chronic kidney disease (CKD). Controversial results were reported in experimental non-diabetic models of CKD. Therefore, we examined empagliflozin effects in three CKD models, namely, in fawn-hooded hypertensive (FHH) rats, uninephrectomized salt-loaded (UNX + HS) rats, and in rats with Goldblatt hypertension (two-kidney, one-clip 2K1C) that were either untreated or treated with empagliflozin (10 mg/kg/day) for eight weeks. Plethysmography blood pressure (BP) was recorded weekly, and renal parameters (proteinuria, plasma urea, creatinine clearance, and sodium excretion) were analyzed three times during the experiment. At the end of the study, blood pressure was also measured directly. Markers of oxidative stress (TBARS) and inflammation (MCP-1) were analyzed in kidney and plasma, respectively. Body weight and visceral adiposity were reduced by empagliflozin in FHH rats, without a significant effect on BP. Experimentally induced CKD (UNX + HS and 2K1C) was associated with a substantial increase in BP and relative heart and kidney weights. Empagliflozin influenced neither visceral adiposity nor BP in these two models. Although empagliflozin increased sodium excretion, suggesting effective SGLT-2 inhibition, it did not affect diuresis in any experimental model. Unexpectedly, empagliflozin did not provide renoprotection because proteinuria, plasma urea, and plasma creatinine were not lowered by empagliflozin treatment in all three CKD models. In line with these results, empagliflozin treatment did not decrease TBARS or MCP-1 levels in either model. In conclusion, empagliflozin did not provide the expected beneficial effects on kidney function in experimental models of CKD.

• Klíčová slova
• SGLT-2 inhibition, fawn-hooded hypertensive rat, one-clip hypertension, proteinuria, two-kidney, uninephrectomized salt-loaded,
• Publikační typ
• časopisecké články MeSH

The effects of early sympathectomy on the development of salt hypertension were studied in prepubertal and adult rats with hereditary diabetes insipidus (DI). Early guanethidine administration caused a pronounced and long-term destruction of sympathetic nervous system (SNS) in Brattleboro rats in which blood pressure (BP) was significantly decreased until the age of 22 weeks. This SNS impairment did not abolish the age-dependent BP response of salt-loaded rats that was still greater in young than in adult sympathectomized DI rats. BP of young uninephrectomized DI rats was higher in the late than in the early phase of salt hypertension development. The early sympathectomy lowered BP and increased mortality in all groups of saline drinking DI rats except young uninephrectomized animals in which hypertensive response was attenuated but not prevented. It could be suggested that 1) increased BP response of young rats to high salt intake occurs even in animals with attenuated principal pressor systems, 2) the effects of early sympathectomy on the development of salt hypertension depend on the actual hemodynamic pattern, and 3) moderate BP increase might be a part of homeostatic mechanisms defending the organism threatened by chronic salt overload.

• MeSH
• chlorid sodný škodlivé účinky   MeSH
• guanethidin MeSH
• hypertenze etiologie   metabolismus   terapie   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• nefrektomie MeSH
• potkani Brattleboro MeSH
• stárnutí fyziologie   MeSH
• sympatektomie chemická MeSH
• sympatický nervový systém fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chlorid sodný MeSH
• guanethidin MeSH