Dapagliflozin reduces systolic blood pressure and modulates vasoactive factors
Dapagliflozin reduces systolic blood pressure and modulates vasoactive factors
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DOI：
10.1111/dom.14377
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发表时间：
2021-04-11
影响因子：
5.8
通讯作者：
Dandona, Paresh
中科院分区：
文献类型：
--
作者：
Ghanim, Husam;Batra, Manav;Dandona, Paresh
Aim To investigate the mechanisms underlying improvements in blood pressure (BP) and congestive heart failure outcomes following treatment with dapagliflozin, a sodium-glucose co-transporter-2 inhibitor.Research Design and Methods A total of 52 patients with type 2 diabetes (T2D) with an HbA1c of less than 8% participated in this prospective, double-blind and placebo-controlled study. Patients were randomized (1:1) to either dapagliflozin 10 mg daily or placebo for 12 weeks. Half the patients were also monitored for 6 h following their first dose for acute effects on BP. Blood and urine samples were collected and levels of angiotensinogen, angiotensin II, renin, aldosterone, endothelin-1, atrial natriuretic peptide (ANP), brain natriuretic peptide, cyclic adenosine monophosphate, cyclic guanosine monophosphate (cGMP) and neprilysin were measured. The expression of angiotensin-converting enzyme, guanylate cyclase and phosphodiesterase 5 (PDE5) was measured in circulating mononuclear cells (MNC).Results A total of 24 and 23 patients receiving dapagliflozin and placebo, respectively, completed the 12-week study. Systolic BP decreased significantly, compared with placebo, both after single-dose (by 7 +/- 3 mmHg) and 12-week (by 7 +/- 2 mmHg) treatment with dapagliflozin. Dapagliflozin suppressed angiotensin II and angiotensinogen (by 10.5 +/- 2.1 and 1.45 +/- 0.42 mu g/mL, respectively) and increased ANP and cGMP (by 34 +/- 11 and 29 +/- 11 pmol/mL, respectively) compared with the placebo group. cGMP levels also increased acutely following a single dose of dapagliflozin. Dapagliflozin also suppressed PDE5 expression by 26% +/- 11% in MNC. There were no changes observed in the other vasoactive mediators investigated.Conclusions Dapagliflozin administration in T2D resulted in both acute and chronic reduction in systolic BP, a reduction in vasoconstrictors and an increase in vasodilators. These changes may potentially contribute to its antihypertensive effects and its benefits in congestive cardiac failure.
