A failure to denervate? An integrative assessment of blood pressure regulation in SYMPLICITY HTN-III participants

      Background. A failure to effectively denervate the renal sympathetic nerves has been proposed as a possible explanation for the lack of effect on BP in the SYMPLICITY HTN-III trial. However, no mechanisms of BP regulation were assessed, making it difficult to determine if the procedure reduced sympathetic nerve activity (SNA). Aim. To assess SNA and key regulators of BP in participants from the SYMPLICITY HTN-III study. Methods. Nine patients (55.6±7.2yrs, n=8 male) with Resistant Hypertension, treated with 4.9±1.2 antihypertensive drugs were studied after completion of their participation in SYMPLICITY III. After 20 min of quiet rest cardiac output (C2H2 rebreathing method, Qc), heart rate (ECG) and BP (auscultatory) were measured. Total peripheral resistance (TPR) was calculated from mean arterial pressure and Qc. SNA was measured using the microneurography technique (muscle SNA), and the 24hr urine excretion of norepinephrine (renal SNA) and epinerphrine (sypathoadrenal function). Investigators involved in data collection and analysis were blinded to group allocation. We have not broken the blinding as 6 more subjects will be studied. Results. In patients with a systolic BP of <140mmHg, Qc and MSNA burst frequency were lower than patients with systolic BP of ≥140mmHg (Table 1). TPR, and urinary norepinephrine and epinephrine excretion were similar between groups. Burst incidence was higher in the group with lower systolic BP because heart rate was lower. Conclusions. These preliminary findings suggest that SNA remains elevated despite improved BP control in some patients. Lower BP was associated with lower Qc, indicating blood volume may be lower through pressure natriuresis.
      Table 1Comparison of HTN-III patients with normal and elevated BP.
      Systolic BP <140mmHg, n=4 Systolic BP ≥140mmHg, n=5
      Systolic BP, mmHg 121±17 151±10
      Diastolic BP, mmHg 72±14 90±8
      Qc, l/min indexed to BSA 2.2±0.3 2.8±0.4
      Heart Rate, bpm 70±21 78±11
      TPR, dyn.s.cm5 1364±268 1405±241
      Burst frequency, burst min 40.3±5.8 46.7±21.4
      Burst incidence, burst/100HB 69.9±25.6 57.3±28.1
      Norepinephrine, μg/g creatinine 33.8±4.8 33.0±16.7
      Epinephrine, μg/g creatinine 2.0±0.0 3.0±0.6
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