Angiotensin type 2 receptors in the intermediolateral cell column of the spinal cord: Negative regulation of sympathetic nerve activity and blood pressure

Background Sodium‐glucose cotransporter 2 inhibitors improve cardiovascular outcomes in patients with diabetes with and without heart failure (HF). However, their influence on sympathetic nerve activity (SNA) remains unclear. The purpose of this study was to evaluate the effect of sodium‐glucose cotransporter 2 inhibitors on SNA and compare the responses of SNA to sodium‐glucose cotransporter 2 inhibitors in patients with type 2 diabetes with and without HF. Methods and Results Eighteen patients with type 2 diabetes, 10 with HF (65.4±3.68 years) and 8 without HF (63.3±3.62 years), were included. Muscle SNA (MSNA), heart rate, and blood pressure were recorded before and 12 weeks after administration of dapagliflozin (5 mg/day). Sympathetic and cardiovagal baroreflex sensitivity were simultaneously calculated. Brain natriuretic peptide level increased significantly at baseline in patients with HF than those without HF, while MSNA, blood pressure, and hemoglobin A1c did not differ between the 2 groups. Fasting blood glucose and homeostatic model assessment of insulin resistance did not change in either group after administering dapagliflozin. MSNA decreased significantly in both groups. However, the reduction in MSNA was significantly higher in patients with HF than patients with non‐HF (−20.2±3.46 versus −9.38±3.65 bursts/100 heartbeats; P =0.049), which was concordant with the decrease in brain natriuretic peptide. Conclusions Dapagliflozin significantly decreased MSNA in patients with type 2 diabetes regardless of its blood glucose‐lowering effect. Moreover, the reduction in MSNA was more prominent in patients with HF than in patients with non‐HF. These results indicate that the cardioprotective effects of sodium‐glucose cotransporter 2 inhibitors may, in part, be attributed to improved SNA.

Download Full-text

1417Effect of sodium glucose cotransporter 2 inhibitor on sympathetic nerve activity in type 2 diabetes mellitus patients

European Heart Journal ◽

10.1093/eurheartj/ehz748.0064 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Cited By ~ 1

Author(s):

T Hamaoka ◽

H Murai ◽

H Sugimoto ◽

Y Mukai ◽

Y Okabe ◽

...

Keyword(s):

Blood Pressure ◽

Blood Glucose ◽

Sympathetic Nerve ◽

Baroreflex Sensitivity ◽

Sympathetic Nerve Activity ◽

Sglt2 Inhibitor ◽

Nerve Activity ◽

Type 2 Dm ◽

Sodium Glucose Cotransporter

Abstract Background Diabetes mellitus (DM) is a well-known risk factor for cardiovascular diseases. Augmented sympathetic nerve activity plays an important role in the progressive worsening disease severity. Most of anti-diabetic drugs were demonstrated to not only decrease blood glucose, but also increase sympathetic nerve activity. Recently, it has been reported that sodium glucose cotransporter 2 (SGLT2) inhibitor has beneficial effects on cardiovascular events in spite of the decrease in blood glucose in type 2 DM patients. The underlying mechanisms remain speculative; however, it is assumed that SGLT2 inhibitor would improve sympathetic nerve activity in type 2 DM patients. Purpose The purpose of this study was to evaluate the effect of SGLT2 inhibitor on sympathetic nerve activity in type 2 DM patients. Methods This study was designed as the prospective single-arm study. Type2 DM patients whose HbA1c >7.0% with at least one atherosclerotic risk factors (Hypertension, obesity, smoking history, aging ...) were included. Patients who had renal failure (eGFR<45ml/min/1.73m2) or high age patients (>80 years old) were excluded. We measured blood glucose, HbA1c and blood insulin concentration at baseline and 12 weeks after treatment of dapagliflozin (5mg/day). Muscle sympathetic nerve activity (MSNA) was applied to scrutinize accurate sympathetic nerve activity in type 2 DM patients. Also, baroreflex sensitivity was calculated by examining the relationship between MSNA and beat to beat diastolic blood pressure. Results Eleven type2 DM patients were included in this study. Body mass index, blood pressure, HbA1c and blood insulin concentration tended to decrease at 12weeks after dapagliflozin (body mass index: 27.2±6.3 vs. 24.9±3.2 kg/m2. systolic blood pressure: 121±12.3 vs. 118±13.6 mmHg. diastolic blood pressure: 74.3±6.3 vs. 72.5±7.6 mmHg. HbA1c: 7.6±0.3 vs. 7.2±0.7%. insulin: 9.7±7.2 vs. 8.8±5.1 μU/ml). Dapagliflozin significantly decrease MSNA and heart rate compared to baseline (46.7±7.5 vs. 38.6±6.9 bursts/minute, P<0.05. Heart rate: 80.6±8.5 vs. 72.8±7.4 beats per minute, P<0.05). However, there is no interaction between the reduction in MSNA and baroreflex sensitivity or insulin resistance. 12 weeks administration decreased MSNA Conclusion Our data demonstrated that dapagliflozin significantly decreased MSNA and HR beyond the lowering effect of blood glucose in type2 DM patients. These results indicate the favorable effect of SGLT2 inhibitor might be, in part, attributed to the improvement in sympathetic nerve activity.

Download Full-text

Arterial baroreflex control of sympathetic nerve activity and heart rate in patients with type 2 diabetes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00384.2016 ◽

2016 ◽

Vol 311 (5) ◽

pp. H1170-H1179 ◽

Cited By ~ 24

Author(s):

Seth W. Holwerda ◽

Lauro C. Vianna ◽

Robert M. Restaino ◽

Kunal Chaudhary ◽

Colin N. Young ◽

...

Keyword(s):

Blood Pressure ◽

Type 2 Diabetes ◽

Heart Rate ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Group Differences ◽

Arterial Baroreflex ◽

Nerve Activity ◽

Baroreflex Control

Despite greater blood pressure reactivity to acute cardiovascular stressors and a higher prevalence of hypertension in type 2 diabetes (T2D) patients, limited information is available regarding arterial baroreflex (ABR) control in T2D. We hypothesized that ABR control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) are attenuated in T2D patients. Seventeen T2D patients (50 ± 2 yr; 31 ± 1 kg/m2), 9 weight-matched controls (WM-CON, 46 ± 2 yr; 32 ± 2 kg/m2) and 10 lean controls (Lean-CON, 49 ± 3 yr; 23 ± 1 kg/m2), underwent bolus infusions of sodium nitroprusside (100 μg) followed 60 s later by phenylephrine (150 μg) and weighted linear regression performed. No group differences in overall sympathetic baroreflex gain were observed (T2D: −2.5 ± 0.3 vs. WM-CON: −2.6 ± 0.2 vs. Lean-CON: −2.7 ± 0.4 arbitrary units·beat·mmHg−1, P > 0.05) or in sympathetic baroreflex gain when derived separately during blood pressure (BP) falls (nitroprusside) and BP rises (phenylephrine). In contrast, overall cardiac baroreflex gain was reduced in T2D patients compared with Lean-CON (T2D: 8.2 ± 1.5 vs. Lean-CON: 15.6 ± 2.9 ms·mmHg−1, P < 0.05) and also tended to be reduced in WM-CON (9.3 ± 1.9 ms·mmHg−1) compared with Lean-CON ( P = 0.059). Likewise, during BP rises, cardiac baroreflex gain was reduced in T2D patients and weight-matched controls compared with lean controls ( P < 0.05), whereas no group differences were found during BP falls ( P > 0.05). Sympathetic and cardiac ABR gains were comparable between normotensive and hypertensive T2D patients ( P > 0.05). These findings suggest preserved ABR control of MSNA in T2D patients compared with both obese and lean age-matched counterparts, with a selective impairment in ABR HR control in T2D that may be related to obesity.

Download Full-text