title: Arterial pressure lability is improved by sodium-glucose cotransporter 2 inhibitor in streptozotocin-induced diabetic rats.
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.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Collaborative Research Institute of Innovative Therapeutics for Cardiovascular Diseases, Kyushu University Center for Disruptive Cardiovascular Medicine, Fukuoka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shinohara
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Takesue
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Shibata
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.|Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sonoda
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.|Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan.
authors.forename: Toyoshi
authors.initials: T
authors.lastname: Inoguchi
authors.affiliation: Kyushu University Center for Disruptive Cardiovascular Medicine, Fukuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsui
authors.affiliation: Department of Advanced Cardiovascular Regulation and Therapeutics, Kyushu University Center for Disruptive Cardiovascular Medicine, Fukuoka, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects* / Q000502:physiology; D017704:Baroreflex / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013311:Streptozocin
chemical_list: D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013311:Streptozocin