Effects of dapagliflozin administration under sustained arterial hypertension
A C C Santos, G Brandao, E P B Ojopi, D H S Campos, A P S Marreiros, E A Rodrigues, L U Pagan, P P Santos, R A Coelho, M V M C Pinheiro, G M Ohara, P K Becaro, A D Muniz, K Okoshi, M P OkoshiAbstract
Introduction
Systemic arterial hypertension (SAH) is a major cause of cardiac remodeling and heart failure with both preserved and reduced ejection fraction. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are recommended for heart failure treatment. The effects of SGLT2 inhibitors on cardiac remodeling under sustained arterial hypertension have not been established.
Purpose
To evaluate the effects of the SGLT2 inhibitor dapagliflozin (DAPA) on hypertension and cardiac remodeling in middle aged-spontaneous hypertensive rats (SHR).
Methods
Male SHR and normotensive Wistar rats aged 14 months were assigned into four groups: Control (n=14); Control-DAPA (n=14); SHR (n=15); and SHR-DAPA (n=14). The treated groups received DAPA added to the rat chow at a dosage of 10 mg/kg/day for 12 weeks. Before treatment, echocardiograms were performed to assure homogeneity between groups (data not shown). At the end of the study, structural heart and functional left ventricular parameters were assessed by echocardiogram. Caudal blood pressure was evaluated by pletismography before and after treatment. Statistical analysis: two-way ANOVA and Bonferroni or Kruskal–Wallis and Dunn’s test, and repeated measures ANOVA.
Results
Blood pressure was higher in SHR and SHR-DAPA than their controls. Blood pressure was higher at the end of the experiment than the initial evaluation in SHR and SHR-DAPA groups and did not differ between SHR-DAPA and SHR (Table 1). Body weight was lower in Control-DAPA than Control and lower in SHR and SHR-DAPA than their controls; no difference was observed between SHR-DAPA and SHR. Both SHR-DAPA and SHR had left atrium dilation, concentric left ventricle (LV) hypertrophy, and diastolic dysfunction. Ejection fraction did not differ between groups. Except for a significantly higher tissue Doppler imaging (TDI) of the mean systolic velocity of the mitral annulus (mean S’) in SHR-DAPA than SHR, no differences were observed between SHR-DAPA and SHR groups (Table 2).
Conclusion
Long-term use of dapagliflozin does not modulate body weight and caudal blood pressure in middle-aged-spontaneously hypertensive rats under sustained hypertension. Cardiac remodeling is not changed by dapagliflozin, except for a slightly improvement in TDI mean S’ in the treated SHR group.