Nitric Oxide Dysfunction in Low Flow POTS

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One variant of postural tachycardia syndrome (POTS), designated low flow POTS, is associated with decreased peripheral blood flow related to impaired local vascular regulation.

To investigate the hypothesis that microvascular endothelial dysfunction produces decreased peripheral blood flow in low flow POTS we performed experiments using laser Doppler flowmetry (LDF) combined with iontophoresis in 15 low flow POTS patients, 17 normal flow POTS patients, and 13 healthy reference volunteers varying in age from 14 and 22 years. We tested whether alpha adrenergic vasoregulation was impaired using iontophoretic delivery of tyramine, phentolamine, and bretylium followed by a norepinephrine dose-response. We tested endothelial dependent and independent receptor mediated vasodilation by measuring acetylcholine and sodium nitroprusside dose responses. We tested whether nitric oxide dependent vasodilation was different in these groups by testing the local thermal hyperemic response to saline used as a reference compared with the NOS inhibitor L-NAME.

Adrenergic and receptor dependent cutaneous vasoregulation was similar for low flow POTS, normal flow POTS and reference subjects. Thermal hyperemia produced distinctly different findings: there was marked attenuation of the NO sensitive plateau during prolonged heating which was insensitive to L-NAME in low flow POTS. The pattern of thermal hyperemia response in low flow POTS during saline administration resembled the pattern in reference subjects during L-NAME administration and was minimally affected by L-NAME.

The data suggest that flow dependent nitric oxide release is reduced in low flow POTS. This may account for local flow regulation abnormalities.




Table 1 Patient Dimensions and Resting Hemodynamic Data






Low Flow

Normal Flow

Body Surface Area (M2)




Weight (kg)




Height (cm)




Heart Rate




MAP Right Arm (mmHg)




MAP Right Leg (mmHg)




Venous Occlusion plethysmography blood flow




Laser Doppler Flow (pfu)




*=p<.05 compared to reference subjects. =p<.05 compared to normal flow subjects. A simple Bonferroni correction was applied throughout and results only regarded as significant if they exceed 0.05.



The figure shows representative tracings of the response to local heating to 43oC.

The tracing is biphasic. There is an initial peak, thought to be related to the neurogenic inflammatory response, followed by a higher plateau, which is believed to be related to flow mediated NO-dependent vasodilation.




The figure shows the dose response to norepinephrine iontophoresis after bretylium had been administered to the same site. There are no significant differences among POTS patients or reference subjects.





The figure depicts the response to additional alpha adrenergic agonists and antagonists. The left panel shows the maximal LDF with bretylium, the middle shows the maximum LDF response to phentolamine, the right panel shows the response to preheating (dark bars) followed by tyramine (lighter bars). The only significant difference is a decrease in the pre-tyramine heating response in low flow POTS.


The figure  depicts the response to different doses of acetylcholine, an endothelial dependent vasodilator, in the left panel, and the responses to sodium nitroprusside, an endothelial independent vasodilator in the right panel. There are no differences among the groups with the exception that baseline low flow POTS LDF is decreased in both panels.


The top panel shows saline or L-NAME administered to a representative reference subject by iontophoresis followed by local heating to 43oC. An initial peak occurs and is followed by a higher plateau. Iontophoretic administration of L-NAME slightly blunts the initial peak and markedly decreases the plateau phase. The bottom panel shows local heating followed by saline or L-NAME in a representative low flow POTS patient. The initial peak is present but there is marked attenuation of the NO-dependent plateau, even after saline, which resembles blunting by the nitric oxide inhibitor L-NAME. Iontophoretic administration of L-NAME minimally blunts the initial peak but has no additional effect on the plateau phase because of pre-existent impairment of NO release.


The figure  shows averaged data for local heating experiments. The top panel shows data for saline administration, the bottom panel shows data for L-NAME administration. Reference subjects are solid black, low flow POTS are white stripes, normal flow POTS are solid grey. The data indicate greater perfusion in heated saline reference subjects and normal flow POTS patients. L-NAME results are similar for all groups and are not different from data obtained during saline in low flow POTS patients.






Exercise Intolerance- the Exercise Pressor Reflex in POTS
Skeletal Muscle Pump
Normal Leg Venous Capacitance
Postural Neurocognitive
Splanchnic Pooling in Normal Flow POTS
Nitric Oxide Dysfunction in Low Flow POTS
Angiotensin-II in POTS
Decreased Upright Cerebral Blood Flow and Cerebral Autoregulation in POTS
Postural Hyperpnea
Nitric Oxide is Decreased in Angiotensin-II dependent Low flow POTS but increased along with Splanchnic pooling Neuropathic POTS
Local Vascular Responses in POTS
Microvascular Filtration in High Flow POTS
POTS as Thoracic Hypovolemia