Altered systemic hemodynamic and baroreflex response to angiotensin II in postural tachycardia syndrome

Abstract

Background: Postural tachycardia syndrome (POTS) is characterized by excessive orthostatic tachycardia and significant functional disability. We have previously found that patients with POTS have increases in plasma angiotensin II (Ang II) that are twice as high as healthy subjects despite normal blood pressures (BPs). In this study, we assess systemic and renal hemodynamic and functional responses to Ang II infusion in patients with POTS compared with healthy controls.

Methods and results: Following a 3-day sodium-controlled diet, we infused Ang II (3 ng/kg per minute) for 1 hour in patients with POTS (n=15) and healthy controls (n=13) in the supine position. All study subjects were women with normal BP. Ages were similar for patients with POTS and controls (mean±SEM, 30±2 versus 26±1 years; P=0.11). We measured the changes from baseline mean arterial pressure, renal plasma flow, plasma renin activity, aldosterone, urine sodium, and baroreflex sensitivity in both groups. In response to Ang II infusion, patients with POTS had a blunted increase compared with controls in mean arterial pressure (10±1 versus 14±1 mm Hg, P=0.01) and diastolic BP (9±1 versus 13±1 mm Hg, P=0.01) but not systolic BP (13±2 versus 15±2 mm Hg, P=0.40). Renal plasma flow decreased similarly with Ang II infusion in patients with POTS versus controls (-166±20 versus -181±17 mL/min per 1.73 kg/m(2), P=0.58). Postinfusion, the decrease in plasma renin activity (-0.9±0.2 versus -0.6±0.2 ng/mL per hour, P=0.43) and the increase in aldosterone (17±1 versus 15±2 pg/mL, P=0.34) were similar in both groups. The decrease in urine sodium excretion was similar in patients with POTS and controls (-49±12 versus -60±16 mEq/g creatinine, P=0.55). The spontaneous baroreflex sensitivity at baseline was significantly lower in patients with POTS compared with controls (10.1±1.2 versus 16.8±1.5 ms/mm Hg, P=0.003), and it was further reduced with Ang II infusion.

Conclusions: Patients with POTS have blunted vasopressor response to Ang II and impaired baroreflex function. This impaired vasoconstrictive response might be exaggerated with upright posture and may contribute to the subsequent orthostatic tachycardia that is the hallmark of this disorder. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00962949.

Conflict of interest statement

Conflict of Interest Disclosures: None

Figures

Figure 1

The net increase in systolic blood pressure (SBP; panel A), diastolic blood pressure (DBP; panel B) and mean arterial pressure (MAP; panel C) from baseline in response to Ang II infusion in POTS patients (solid line) and control subjects (dashed line). The pressor dose (3 ng/kg/min) was started at time zero. The DBP and MAP responses were significantly different between the two groups.

Figure 2

The change in renal plasma flow (RPF; panel A) and urine sodium excretion corrected for creatinine (panel B) at baseline (base) and in response to Ang II infusion (post). Ang II decreased RPF and increased sodium reabsorption in both POTS patients (black bars) and controls (gray bars) to a similar extent.

Figure 3

The response of plasma renin activity (PRA; panel A) and aldosterone (panel B) were similar between POTS (black bars) and controls (gray bars) at baseline (base) and post-infusion (post).

Figure 4

Plasma Ang II level at baseline was 2 fold higher in POTS compared to control (Panel A). The increase in plasma Ang II levels following Ang II infusion (Panel B) was similar between POTS (black bars) and controls (gray bars).

Figure 5

Baseline baroreflex sensitivity (BRS) calculated with the sequence technique (BRS-down) was significantly lower at baseline in POTS patients compared to control. In response to Ang II infusion the BRS decreased significantly in both groups. The mean reduction in BRS was not different between POTS and control. POTS (black bars) and controls (gray bars).