Dapagliflozin Reduces Systolic Blood Pressure and Modulates
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Mechanisms underlying the improvements in blood pressure (BP) and congestive heart failure outcomes following treatment with dapagliflozin are not fully understood. Researchers hypothesized that vasoactive mediators may be involved.

52 type 2 diabetes patients (T2DM) with HbA1c 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 hours 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 (BNP), Cyclic adenosine monophosphate (cAMP), Cyclic guanosine monophosphate (cGMP) and neprilysin were measured. Expression of angiotensin converting enzyme, guanylate cyclase and phosphodiesterase 5 (PDE5) were measured in circulating mononuclear cells (MNC).

Results:
-- 24 and 23 patients receiving dapagliflozin and placebo, respectively, completed the 12 weeks' study.

-- Systolic BP fell significantly, compared to placebo, both after a 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 pg/mL and 1.45 ± 0.42 µg/mL, respectively) and increased ANP and cGMP (by 34±11 pg/mL and 29 ± 11 pmol/mL, respectively) compared to placebo group.

-- cGMP levels also increased acutely following a single dose of dapagliflozin.

-- Dapagliflozin also suppressed PDE5 expression by 26 ± 11% in MNC. There was no change in the other vasoactive mediators investigated.

Conclusively, Dapagliflozin administration to T2DM 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 anti-hypertensive effects and its benefits in congestive cardiac failure.

Source: https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14377?af=R
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