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Arterial pressure lability is improved by sodium-glucose cotransporter 2 inhibitor in streptozotocin-induced diabetic rats.

Arterial pressure lability is improved by sodium-glucose cotransporter 2 inhibitor in streptozotocin-induced diabetic rats.
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Yoshikawa T, Kishi T, Shinohara K, Takesue K, Shibata R, Sonoda N, Inoguchi T, Sunagawa K, Tsutsui H, Hirooka Y,


Yoshikawa T, Kishi T, Shinohara K, Takesue K, Shibata R, Sonoda N, Inoguchi T, Sunagawa K, Tsutsui H, Hirooka Y, (click to view)

Yoshikawa T, Kishi T, Shinohara K, Takesue K, Shibata R, Sonoda N, Inoguchi T, Sunagawa K, Tsutsui H, Hirooka Y,

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Hypertension research : official journal of the Japanese Society of Hypertension 2017 02 16() doi 10.1038/hr.2017.14
Abstract

To prevent cardiovascular events in patients with diabetes mellitus (DM), it is essential to reduce arterial pressure (AP). Sodium-glucose cotransporter 2 inhibitor (SGLT2i) prevents cardiovascular events via the depressor response in patients with DM. In the present study, we examined whether SGLT2i ameliorates AP lability in DM rats. Ten-week-old male Sprague-Dawley rats were administered a single intravenous injection of streptozotocin (50 mg kg(-1)) and were divided into three groups treated with low-dose SGLT2i, vehicle (VEH) or subcutaneously implanted insulin pellets (SGLT2i, VEH and Insulin group, respectively) for 14 days. SGLT2i reduced blood glucose, but its effect was lower than that of insulin. The telemetered mean AP at the end of the experiment did not differ among the SGLT2i, Insulin and VEH groups (83±7 vs. 98±9 vs. 90±8 mm Hg, respectively, n=5 for each). The standard deviation of AP as the index of lability was significantly smaller during the active period in the SGLT2i group than in the VEH group (5.6±0.5 vs. 7.0±0.7 mm Hg, n=5 for each, P<0.05). Sympathetic nerve activity during the active period was significantly lower in the SGLT2i group than in the VEH group. Baroreflex sensitivity (BRS) was significantly higher in the SGLT2i group than in the VEH group. The standard deviation of AP and sympathoexcitation did not differ between the Insulin and VEH groups. In conclusion, SGLT2i at a non-depressor dose ameliorated the AP lability associated with sympathoinhibition during the active period and improved the BRS in streptozotocin-induced DM rats.Hypertension Research advance online publication, 16 February 2017; doi:10.1038/hr.2017.14.

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