Arterial perivascular adipose tissue (PVAT) can elicit vasodilator signals complementary to those elicited by the endothelium in SHRSP.Z-Lepr^fa/IzmDmcr (SHRSP.ZF) rats, an animal model of metabolic syndrome (MetS). Here, we tested whether a glucose cotransporter 2 inhibitor (SGLT2-i; tofogliflozin) increased this PVAT effect to prevent the deterioration of cardiac function in aging SHRSP.ZF rats. Tofogliflozin treatments (1 or 10 mg/kg/day) or vehicle (control) were administered for 10 weeks by oral gavage to SHRSP.ZF rats, starting at 13 weeks of age. At 23 weeks of age, glucose levels in the serum and urine (24 h after the last administration) were determined using commercial kits. Vasodilator responsiveness of PVAT-surrounded or PVAT-free superior mesenteric arteries was determined using acetylcholine with organ-bath methods. Cardiac ventricular function and coronary flow were determined using Langendorff heart preparations. Serum and urine glucose levels in SGLT2-i treatment groups did not differ from those in the controls, but the ratios of glycated to non-glycated albumin were lower than those in the controls. Tofogliflozin treatments did not alter relaxations in the presence of PVAT or affect relaxations of PVAT-free arteries. Left ventricular systolic pressures, maximum rate of pressure decline, and coronary flow in ex vivo hearts did not differ among the treatment groups. PVAT effects and cardiac dysfunction were not altered by tofogliflozin treatment in SHRSP.ZF rats with MetS. These results do not provide strong evidence to support the use of SGLT2-i as a cardiovascular protective therapy in MetS, which occurs prior to the onset of type 2 diabetes.

动脉血管周围脂肪组织 (PVAT) 可引发血管扩张信号，与 SHRSP 中内皮引发的信号互补。Z- Lepr ^fa/IzmDmcr (SHRSP.ZF) 大鼠，一种代谢综合征 (MetS) 的动物模型。在这里，我们测试了葡萄糖协同转运蛋白 2 抑制剂 (SGLT2-i; tofogliflozin) 是否增加了这种 PVAT 作用，以防止衰老 SHRSP.ZF 大鼠的心脏功能恶化。Tofogliflozin 治疗（1 或 10 mg/kg/天）或载体（对照）通过口服管饲法对 SHRSP.ZF 大鼠给药 10 周，从 13 周龄开始。在 23 周龄时，使用商业试剂盒测定血清和尿液中的葡萄糖水平（最后一次给药后 24 小时）。使用乙酰胆碱和器官浴法测定 PVAT 周围或无 PVAT 的肠系膜上动脉的血管扩张剂反应性。使用 Langendorff 心脏制剂测定心室功能和冠状动脉血流。SGLT2-i 治疗组的血清和尿葡萄糖水平与对照组没有差异，但糖化白蛋白与非糖化白蛋白的比率低于对照组。Tofogliflozin 治疗不会改变存在 PVAT 时的松弛或影响无 PVAT 动脉的松弛。左心室收缩压、最大压力下降率和冠状动脉血流离体心脏在治疗组之间没有差异。在患有 MetS 的 SHRSP.ZF 大鼠中，tofgliflozin 治疗未改变 PVAT 效应和心功能障碍。这些结果没有提供强有力的证据来支持使用 SGLT2-i 作为 MetS 的心血管保护性治疗，MetS 发生在 2 型糖尿病发病之前。