Altered Sympathetic Nervous Reactivity and Norepinephrine Transporter Expression in Patients With Postural Tachycardia Syndrome

Abstract

Background-Clinical observations in patients with postural tachycardia syndrome (POTS) suggest abnormal sympathetic nervous system activity and a dysfunction of the norepinephrine (NE) transporter (NET). Methods and Results-We examined sympathetic nervous system responses to head-up tilt by combining NE plasma kinetics measurements and muscle sympathetic nerve activity recordings and by quantifying NET protein content in peripheral sympathetic nerves in patients with POTS compared with that in controls. POTS patients had an elevated heart rate during supine rest (81Ϯ2 bpm versus 66Ϯ2 bpm in healthy subjects [HS], PϽ0.01). Head-up tilt to 40°i nduced a greater rise in heart rate in patients with POTS (ϩ24Ϯ4 bpm versus ϩ13Ϯ2 bpm in HS, PϽ0.001). During rest in the supine position, muscle sympathetic nerve activity, arterial NE concentration, and whole-body NE spillover to plasma were similar in both groups. Muscle sympathetic nerve activity response to head-up tilt was greater in the POTS group (ϩ29Ϯ3 bursts/min in patients with POTS and ϩ13Ϯ2 bursts/min in HS, PϽ0.001), but the NE spillover rise was similar in both groups (51% in the POTS subjects and 50% in the HS). Western blot analysis of NET protein extracted from forearm vein biopsies in patients with POTS and HS demonstrated a decrease in the expression of NET protein in patients with POTS. Conclusion-Patients

Cognitive function, health-related quality of life, and symptoms of depression and anxiety sensitivity are impaired in patients with the postural orthostatic tachycardia syndrome (POTS)

“…It is likely that the association between depression and cognitive performance reflects the underlying neurobiology of depression, with alterations in brain monoamines influencing both depression and cognition (Lambert et al, 2000; Austin et al, 2001; Schmitt et al, 2006; Barton et al, 2008; Wingen et al, 2008; Chalermpalanupap et al, 2013). Noradrenaline transporter (NET) dysfunction is evident in patients with POTS (Shannon et al, 2000; Lambert et al, 2008) and in untreated patients with major depressive disorder (Barton et al, 2007). Interestingly, genetic variation in the NET gene has been associated with deficits in memory and attention in patients with ADHD (Thakur et al, 2012).…”

Sympathetic dysfunction in vasovagal syncope and the postural orthostatic tachycardia syndrome

“…More robust and precise assessment of sympathetic activity by direct measurements of total body and regional noradrenaline spillover have been performed in a few investigations and the results have been variable. Evidence of sympathoexitation was confirmed in one study (Jordan et al, 2002), but not in others (Jacob et al, 1999; Goldstein et al, 2002a; Lambert et al, 2008). The possible hyperadrenergic features of POTS may not be simply due to increased central sympathetic outflow and noradrenaline release but potentially from an augmentation of the sympathetic signal due to enhanced receptor sensitivity or to a reduction in noradrenaline clearance during standing.…”

“…Some investigations (Streeten et al, 1988; Schondorf and Low, 1993; Furlan et al, 1998; Jacob et al, 1999), but not all (Jacob et al, 2000; Lambert et al, 2008), have reported that POTS patients have greater systemic plasma noradrenaline concentrations at rest or during orthostasis compared with healthy controls, suggesting that POTS is associated with a hyperadrenergic state. More robust and precise assessment of sympathetic activity by direct measurements of total body and regional noradrenaline spillover have been performed in a few investigations and the results have been variable.…”

Obesity Paradox in Hypertension

“…Impaired neuronal noradrenaline reuptake, as a solitary identified abnormality in patients with the postural tachycardia syndrome, 70,82 is not associated with heart disease or reduced longevity. Conversely, with the coexistence of impaired norepinephrine reuptake with firing salvos in normal-weight essential hypertension 31,[33][34][35][36] and in depressive illness 42,51,79 and panic disorder, 51,79,80 there is evidence of cardiac risk, 84 even in panic disorder.…”