Dapagliflozin

Twelve-week-old male db/db mice were weighted and then placed in individual metabolic cages. These mice were maintained for 10 days on a 4% HSD to induce hypertension. On day 10, the animals’ blood pressure was measured to confirm the development of hypertension (systolic blood pressure greater than 140 mmHg), and the animals were randomly separated into a control group that received a vehicle (saline) and an experimental group that received 1 mg/kg/day dapagliflozin (MedChemExpress, Junction, NJ, USA) for 14 days at 6 p.m. by oral gavage. Urine samples were collected daily between 9 a.m. and 11 a.m. (reflecting urine produced during the night-time active phase) and between 9 p.m. and 11 p.m. (reflecting urine produced during the day-time inactive phase).

Dapagliflozin was purchased from Med Chem Express (Table S1) and freshly prepared by suspending in corn oil immediately prior to use. To test the effect on the formation of AAA, mice were daily treated with Dapagliflozin at 1 or 5 mg/kg body weight through oral gavage (n = 10 mice for each dose). Additional 10 mice were treated with an equal volume (200 uL) of corn oil as vehicle. All treatments began 1 day before and terminated 14 days after PPE infusion. These doses have been proven effective in published studies [27 (link)–29 (link)]. To assess the effect on the progression of existing AAA, Dapagliflozin (5 mg/kg) or an equal volume of vehicle was administered 4 days following PPE infusion, the time point by which aneurysms are formed in this model and continued for 10 days (n = 10 for each group) [30 ]. Fourteen days after PPE infusion, all mice were euthanized by carbon dioxide inhalation.