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Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness and renal resistive index in type 2
Anna Solini1, Livia Giannini2, Marta Seghieri2
1Department of Surgical, Medical, Molecular and Critical Area Pathology, I-56126, Pisa, Italy. anna.solini@med.unipi.it.
Background:
Sodium-glucose cotransporter-2 inhibitors reduce blood pressure (BP) and renal and cardiovascular events in patients with type 2 diabetes through not fully elucidated mechanisms. Aim of this study was to investigate whether dapagliflozin is able to acutely modify systemic and renal vascular function, as well as putative mechanisms.
Methods:
Neuro-hormonal and vascular variables, together with 24 h diuresis, urinary sodium, glucose, isoprostanes and free-water clearance were assessed before and after a 2-day treatment with dapagliflozin 10 mg QD in sixteen type 2 diabetic patients; data were compared with those obtained in ten patients treated with hydrochlorothiazide 12.5 mg QD. Brachial artery endothelium-dependent and independent vasodilation (by flow-mediated dilation) and pulse wave velocity were assessed. Renal resistive index was obtained at rest and after glyceryl trinitrate administration. Differences were analysed by repeated measures ANOVA, considering treatment as between factor and time as within factor; Bonferroni post hoc comparison test was also used.
Results:
Dapagliflozin decreased systolic BP and induced an increase in 24 h diuresis to a similar extent of hydrochlorothiazide; 24 h urinary glucose and serum magnesium were also increased. 24 h urinary sodium and fasting blood glucose were unchanged. Oxidative stress was reduced, as by a decline in urinary isoprostanes. Flow-mediated dilation was significantly increased (2.8 ± 2.2 to 4.0 ± 2.1%, p < 0.05), and pulse-wave-velocity was reduced (10.1 ± 1.6 to 8.9 ± 1.6 m/s, p < 0.05), even after correction for mean BP. Renal resistive index was reduced (0.62 ± 0.04 to 0.59 ± 0.05, p < 0.05). These vascular modifications were not observed in hydrochlorothiazide-treated individuals.
Conclusions:
An acute treatment with dapagliflozin significantly improves systemic endothelial function, arterial stiffness and renal resistive index; this effect is independent of changes in BP and occurs in the presence of stable natriuresis, suggesting a fast, direct beneficial effect on the vasculature, possibly mediated by oxidative stress reduction.
Insights
Sodium-glucose cotransporter-2 inhibitor dapagliflozin improves vascular function in type 2 diabetes patients. This drug enhances endothelial function and reduces arterial stiffness, suggesting direct vascular benefits beyond blood pressure changes.
Area of Science:
- Cardiology
- Nephrology
- Endocrinology
Background:
- Sodium-glucose cotransporter-2 (SGLT2) inhibitors are known to reduce blood pressure (BP) and cardiovascular events in type 2 diabetes patients.
- The exact mechanisms underlying these benefits are not fully understood.
- This study investigates the acute effects of dapagliflozin on vascular function and potential mechanisms.
Purpose of the Study:
- To assess the acute impact of dapagliflozin on systemic and renal vascular function in type 2 diabetes patients.
- To explore the underlying mechanisms, including oxidative stress and neuro-hormonal changes.
- To compare dapagliflozin's vascular effects with those of hydrochlorothiazide.
Main Methods:
- Sixteen type 2 diabetes patients received dapagliflozin (10 mg QD) for 2 days.
- Vascular parameters including flow-mediated dilation (FMD) and pulse wave velocity (PWV) were measured.
- Renal resistive index, diuresis, urinary sodium, glucose, and isoprostanes were assessed before and after treatment.
Main Results:
- Dapagliflozin significantly improved flow-mediated dilation (2.8% to 4.0%) and reduced pulse wave velocity (10.1 m/s to 8.9 m/s) and renal resistive index (0.62 to 0.59).
- These vascular improvements were independent of changes in mean blood pressure.
- Urinary isoprostanes decreased, indicating reduced oxidative stress.
Conclusions:
- Acute dapagliflozin treatment significantly enhances systemic endothelial function, arterial stiffness, and renal vascular resistance.
- These beneficial vascular effects appear to be direct and rapid, potentially mediated by a reduction in oxidative stress.
- The observed improvements in vascular function were not seen with hydrochlorothiazide treatment.
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