Antihypertensive and metabolic effects of empagliflozin in Ren-2 transgenic rats, an experimental non-diabetic model of hypertension

The new antidiabetic drugs, gliflozins, inhibit sodium-glucose transporter-2 in renal proximal tubules promoting glucose and sodium excretion. This leads not only to a significant improvement of glucose control but also to the reduction of blood pressure and body weight in both diabetic patients and...

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Autores principales:	Silvie Hojná, Hana Rauchová, Hana Malínská, Irena Marková, Martina Hüttl, František Papoušek, Michal Behuliak, Denisa Miklánková, Zdeňka Vaňourková, Jan Neckář, Michaela Kadlecová, Petr Kujal, Josef Zicha, Ivana Vaněčková
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	SGLT-2 inhibitor Cardiac Renal and metabolic parameters Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/e201a9068c7440d880c7984feaa998e8
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spelling	oai:doaj.org-article:e201a9068c7440d880c7984feaa998e82021-11-14T04:28:49ZAntihypertensive and metabolic effects of empagliflozin in Ren-2 transgenic rats, an experimental non-diabetic model of hypertension0753-332210.1016/j.biopha.2021.112246https://doaj.org/article/e201a9068c7440d880c7984feaa998e82021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221010301https://doaj.org/toc/0753-3322The new antidiabetic drugs, gliflozins, inhibit sodium-glucose transporter-2 in renal proximal tubules promoting glucose and sodium excretion. This leads not only to a significant improvement of glucose control but also to the reduction of blood pressure and body weight in both diabetic patients and experimental models. We examined whether these beneficial effects can also be achieved in a non-diabetic hypertensive model, namely in Ren-2 transgenic rats (TGR). Adult 6-month-old hypertensive TGR and their normotensive controls (Hannover Sprague-Dawley rats), were either untreated or treated with empagliflozin (10 mg/kg/day) for two months. Telemetric blood pressure monitoring, renal parameters as well as cardiac function via echocardiography were analyzed during the experiment. At the end of the study, the contribution of major vasoactive systems to blood pressure maintenance was studied. Metabolic parameters and markers of oxidative stress and inflammation were also analyzed. Empagliflozin had no effect on plasma glucose level but partially reduced blood pressure in TGR. Although food consumption was substantially higher in empagliflozin-treated TGR compared to the untreated animals, their body weight and the amount of epididymal and perirenal fat was decreased. Empagliflozin had no effect on proteinuria, but it decreased plasma urea, attenuated renal oxidative stress and temporarily increased urinary urea excretion. Several metabolic (hepatic triglycerides, non-esterified fatty acids, insulin) and inflammatory (TNF-α, leptin) parameters were also improved by empagliflozin treatment. By contrast, echocardiography did not reveal any effect of empagliflozin on cardiac function. In conclusion, empagliflozin exerted beneficial antihypertensive, anti-inflammatory and metabolic effects also in a non-diabetic hypertensive model.Silvie HojnáHana RauchováHana MalínskáIrena MarkováMartina HüttlFrantišek PapoušekMichal BehuliakDenisa MiklánkováZdeňka VaňourkováJan NeckářMichaela KadlecováPetr KujalJosef ZichaIvana VaněčkováElsevierarticleSGLT-2 inhibitorCardiacRenal and metabolic parametersTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112246- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SGLT-2 inhibitor Cardiac Renal and metabolic parameters Therapeutics. Pharmacology RM1-950
spellingShingle	SGLT-2 inhibitor Cardiac Renal and metabolic parameters Therapeutics. Pharmacology RM1-950 Silvie Hojná Hana Rauchová Hana Malínská Irena Marková Martina Hüttl František Papoušek Michal Behuliak Denisa Miklánková Zdeňka Vaňourková Jan Neckář Michaela Kadlecová Petr Kujal Josef Zicha Ivana Vaněčková Antihypertensive and metabolic effects of empagliflozin in Ren-2 transgenic rats, an experimental non-diabetic model of hypertension
description	The new antidiabetic drugs, gliflozins, inhibit sodium-glucose transporter-2 in renal proximal tubules promoting glucose and sodium excretion. This leads not only to a significant improvement of glucose control but also to the reduction of blood pressure and body weight in both diabetic patients and experimental models. We examined whether these beneficial effects can also be achieved in a non-diabetic hypertensive model, namely in Ren-2 transgenic rats (TGR). Adult 6-month-old hypertensive TGR and their normotensive controls (Hannover Sprague-Dawley rats), were either untreated or treated with empagliflozin (10 mg/kg/day) for two months. Telemetric blood pressure monitoring, renal parameters as well as cardiac function via echocardiography were analyzed during the experiment. At the end of the study, the contribution of major vasoactive systems to blood pressure maintenance was studied. Metabolic parameters and markers of oxidative stress and inflammation were also analyzed. Empagliflozin had no effect on plasma glucose level but partially reduced blood pressure in TGR. Although food consumption was substantially higher in empagliflozin-treated TGR compared to the untreated animals, their body weight and the amount of epididymal and perirenal fat was decreased. Empagliflozin had no effect on proteinuria, but it decreased plasma urea, attenuated renal oxidative stress and temporarily increased urinary urea excretion. Several metabolic (hepatic triglycerides, non-esterified fatty acids, insulin) and inflammatory (TNF-α, leptin) parameters were also improved by empagliflozin treatment. By contrast, echocardiography did not reveal any effect of empagliflozin on cardiac function. In conclusion, empagliflozin exerted beneficial antihypertensive, anti-inflammatory and metabolic effects also in a non-diabetic hypertensive model.
format	article
author	Silvie Hojná Hana Rauchová Hana Malínská Irena Marková Martina Hüttl František Papoušek Michal Behuliak Denisa Miklánková Zdeňka Vaňourková Jan Neckář Michaela Kadlecová Petr Kujal Josef Zicha Ivana Vaněčková
author_facet	Silvie Hojná Hana Rauchová Hana Malínská Irena Marková Martina Hüttl František Papoušek Michal Behuliak Denisa Miklánková Zdeňka Vaňourková Jan Neckář Michaela Kadlecová Petr Kujal Josef Zicha Ivana Vaněčková
author_sort	Silvie Hojná
title	Antihypertensive and metabolic effects of empagliflozin in Ren-2 transgenic rats, an experimental non-diabetic model of hypertension
title_short	Antihypertensive and metabolic effects of empagliflozin in Ren-2 transgenic rats, an experimental non-diabetic model of hypertension
title_full	Antihypertensive and metabolic effects of empagliflozin in Ren-2 transgenic rats, an experimental non-diabetic model of hypertension
title_fullStr	Antihypertensive and metabolic effects of empagliflozin in Ren-2 transgenic rats, an experimental non-diabetic model of hypertension
title_full_unstemmed	Antihypertensive and metabolic effects of empagliflozin in Ren-2 transgenic rats, an experimental non-diabetic model of hypertension
title_sort	antihypertensive and metabolic effects of empagliflozin in ren-2 transgenic rats, an experimental non-diabetic model of hypertension
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/e201a9068c7440d880c7984feaa998e8
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Antihypertensive and metabolic effects of empagliflozin in Ren-2 transgenic rats, an experimental non-diabetic model of hypertension

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