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 POTS patients had increases in plasma angiotensin II (Ang II) twice as high as normal subjects despite normal blood pressures. 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/min) for 1 hour in POTS patients (n=15) and healthy controls (n=13) in the supine position. All study subjects were females with normal blood pressure (BP). Ages were similar for POTS and control subjects (30±2 [mean±SEM] vs. 26±1 years; P=0.11). We measured the changes from baseline mean arterial pressure (MAP), renal plasma flow (RPF), plasma renin activity (PRA), aldosterone, urine sodium and baroreflex sensitivity in both groups. In response to Ang II infusion, POTS patients had a blunted increase compared with control subjects in MAP (10±1 mmHg vs. 14±1 mmHg; P=0.01), and diastolic BP (9±1 mmHg vs. 13±1 mmHg; P=0.01), but not systolic BP (13±2 mmHg vs. 15±2 mmHg; P=0.40). Renal plasma flow (RPF) decreased similarly with Ang II infusion in POTS patients and controls (−166±20 vs. −181±17 mL/min/1.73 kg/m2; P=0.58). Post-infusion, the decrease in PRA (−0.9±0.2 vs. −0.6±0.2 ng/mL/h; P=0.43) and the increase in aldosterone (17±1 vs. 15±2 pg/ml; P=0.34) were similar in POTS and controls. The decrease in urine sodium excretion was similar in both POTS and controls (−49±12 vs. −60±16 mEq/g Cr; P=0.55). The spontaneous baroreflex sensitivity at baseline was significantly lower in POTS compared to healthy controls (10.1±1.2 vs. 16.8±1.5 ms/mmHg, 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.

Asymmetries in reciprocal baroreflex mechanisms and chronic pain severity: Focusing on irritable bowel syndrome

“…[83][84][85][86] Pain-related effect on the baroreflex symmetry mechanism, which diminishes tachycardiac baroreflex in response to BP decrease (a putative "pain resilience" mechanism) may determine, as a byproduct, the symptoms of OI and POTS in some patients as one of multiple distinct pathophysiological subtypes within them. 87 Its resilience attribute is concordant with findings of increased orthostatic heart rate response as a biomarker of more universal mechanism of protection against negative affect, chronic pain, and hemorrhage severity. 18,62,88 Chronic pain is also frequently co-morbid with arterial hypertension.…”

“…Chronic pain of different origins including abdomen is frequently co‐morbid with the orthostatic intolerance (OI) and the Postural Tachycardia Syndrome (POTS) . Pain‐related effect on the baroreflex symmetry mechanism, which diminishes tachycardiac baroreflex in response to BP decrease (a putative “pain resilience” mechanism) may determine, as a byproduct, the symptoms of OI and POTS in some patients as one of multiple distinct pathophysiological subtypes within them . Its resilience attribute is concordant with findings of increased orthostatic heart rate response as a biomarker of more universal mechanism of protection against negative affect, chronic pain, and hemorrhage severity .…”

Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome

“…9 The Vanderbilt group has also reported an impaired vascular pressor response to Ang II in patients with POTS. 15 Sodium loading is frequently used to ameliorate some of the cardiovascular symptoms associated with POTS. Such salt loading would normally suppress endogenous Ang II concentrations and concurrently increase the sensitivity of vascular AT1R to their circulating autoantibodies.…”

Postural Orthostatic Tachycardia Syndrome during pregnancy: A systematic review of the literature

“…Postural Orthostatic Tachycardia Syndrome (POTS) is a condition of the autonomic nervous system that is five times more likely to affect women, and occurs most often in child bearing age Raj, 2006;Benrud-Larson et al, 2002;Low et al, 2009). The prevalence of POTS is unknown due to difficulty with diagnosis, however it is estimated that between 500,000 and 3,000,000 Americans are affected (Mar and Raj, 2014;Robertson, 1999;Mustafa et al, 2012;Pavlik et al, 2016). It is characterized by symptoms of orthostatic tachycardia including tachycardia, palpitations, syncope or pre-syncope, light headedness, cognitive dysfunction, nausea, exercise or heat intolerances, and fatigue (Benarroch, 2012;Pavlik et al, 2016).…”