Increased plasma angiotensin II in postural tachycardia syndrome (POTS) is related to reduced blood flow and blood volume

American Journal of Physiology-Heart and Circulatory Physiology

Ocon

Medow

2011

Stewart JM, Ocon AJ, Medow MS. Ascorbate improves circulation in postural tachycardia syndrome. Am J Physiol Heart Circ Physiol 301: H1033-H1042, 2011. First published May 27, 2011 doi:10.1152/ajpheart.00018.2011.-Low flow postural tachycardia syndrome (LFP) is associated with vasoconstriction, reduced cardiac output, increased plasma angiotensin II, reduced bioavailable nitric oxide (NO), and oxidative stress. We tested whether ascorbate would improve cutaneous NO and reduce vasoconstriction when delivered systemically. We used local cutaneous heating to 42°C and laser Doppler flowmetry to assess NO-dependent conductance (%CVCmax) to sodium ascorbate and the systemic hemodynamic response to ascorbic acid in 11 LFP patients and in 8 control subjects (aged 23 Ϯ 2 yr). We perfused intradermal microdialysis catheters with sodium ascorbate (10 mM) or Ringer solution. Predrug heat response was reduced in LFP, particularly the NO-dependent plateau phase (56 Ϯ 6 vs. 88 Ϯ 7%CVCmax). Ascorbate increased baseline skin flow in LFP and control subjects and increased the LFP plateau response (82 Ϯ 6 vs. 92 Ϯ 6 control). Systemic infusion experiments used Finometer and ModelFlow to estimate relative cardiac index (CI) and forearm and calf venous occlusion plethysmography to estimate blood flows, peripheral arterial and venous resistances, and capacitance before and after infusing ascorbic acid. CI increased 40% after ascorbate as did peripheral flows. Peripheral resistances were increased (nearly double control) and decreased by nearly 50% after ascorbate. Calf capacitance and venous resistance were decreased compared with control but normalized with ascorbate. These data provide experimental support for the concept that oxidative stress and reduced NO possibly contribute to vasoconstriction and venoconstriction of LFP. free radicals; vasoconstriction POSTURAL TACHYCARDIA SYNDROME (POTS) accounts for most cases of chronic orthostatic intolerance (21,28,39,47,48). POTS is defined by excessive increase in upright heart rate and symptoms of orthostatic intolerance (39) improving with recumbence. Our laboratory (42) has described a subset of POTS designated "low flow POTS" (LFP) in which there is marked upright tachycardia and circulatory insufficiency even while supine including resting tachycardia, decreased cardiac output (CO), and decreased regional blood flows with peripheral and cutaneous vasoconstriction, findings often ascribed to a hyperadrenergic state (1, 6). A consistent observation has been increased plasma angiotensin II (ANG II; Refs. 40,43,45), which can act locally to decrease bioavailable nitric oxide (NO) by superoxide scavenging to create peroxynitrite (36). ANG II also acts through reactive oxygen species (ROS; Ref. 35) to increase central and peripheral sympathetic activity (9, 52). Both increased ANG II due to deficient ACE2 and decreased bioavailable NO have been demonstrated in LFP during prior experiments using intradermal microdialysis techniques. Experiments made extensive use of the local vasodilator...

Section: Limitationssupporting

confidence: 71%

Section: Subjectsmentioning

confidence: 99%

mentioning

confidence: 99%

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Ascorbate improves circulation in postural tachycardia syndrome

American Journal of Physiology-Heart and Circulatory Physiology

Ocon

Medow

2011

“…Supine CBV is reduced in some patients with POTS 31, 34, 35, 36. This is striking in those patients with evidence for increased supine sympathoexcitation 37.…”

Section: Discussionmentioning

confidence: 96%

Postural Hyperventilation as a Cause of Postural Tachycardia Syndrome: Increased Systemic Vascular Resistance and Decreased Cardiac Output When Upright in All Postural Tachycardia Syndrome Variants

Pianosi

Shaban

et al. 2018

JAHA

BackgroundPostural tachycardia syndrome (POTS) is a heterogeneous condition. We stratified patients previously evaluated for POTS on the basis of supine resting cardiac output (CO) or with the complaint of platypnea or “shortness of breath” during orthostasis. We hypothesize that postural hyperventilation is one cause of POTS and that hyperventilation‐associated POTS occurs when initial reduction in CO is sufficiently large. We also propose that circulatory abnormalities normalize with restoration of CO 2.Methods and ResultsFifty‐eight enrollees with POTS were compared with 16 healthy volunteer controls. Low CO in POTS was defined by a resting supine CO <4 L/min. Patients with shortness of breath had hyperventilation with end tidal CO 2 <30 Torr during head‐up tilt table testing. There were no differences in height or weight between control patients and patients with POTS or differences between the POTS groups. Beat‐to‐beat blood pressure was measured by photoplethysmography, and CO was measured by ModelFlow. Systemic vascular resistance was defined as mean arterial blood pressure/CO. End tidal CO 2 and cerebral blood flow velocity of the middle cerebral artery were only reduced during head‐up tilt in the hyperventilation group, whereas blood pressure was increased compared with control. We corrected the reduced end tidal CO 2 in hyperventilation by addition of exogenous CO 2 into a rebreathing apparatus. With added CO 2, heart rate, blood pressure, CO, and systemic vascular resistance in hyperventilation became similar to control.ConclusionsWe conclude that all POTS is related to decreased CO, decreased central blood volume, and increased systemic vascular resistance and that a variant of POTS is consequent to postural hyperventilation.

“…It has been used to evaluate NO bioavailability (15,26,32). Recently, we observed that plasma angiotensin II (ANG II) is increased in a subset of patients with postural tachycardia syndrome (POTS) (25,27) in whom we demonstrated blunted cutaneous microvascular NO-dependent vasodilation to local heat (18). We further demonstrated that ANG II type 1 receptor (AT 1 R) blockade with losartan corrects the cutaneous NO deficit in these patients (26).…”

mentioning

confidence: 99%

Intradermal angiotensin II administration attenuates the local cutaneous vasodilator heating response

American Journal of Physiology-Heart and Circulatory Physiology

Taneja²,

Raghunath³

et al. 2008

The vasodilation response to local cutaneous heating is nitric oxide (NO) dependent and blunted in postural tachycardia but reversed by angiotensin II (ANG II) type 1 receptor (AT1R) blockade. We tested the hypothesis that a localized infusion of ANG II attenuates vasodilation to local heating in healthy volunteers. We heated the skin of a calf to 42°C and measured local blood flow to assess the percentage of maximum cutaneous vascular conductance (%CVCmax) in eight healthy volunteers aged 19.5-25.5 years. Initially, two experiments were performed; in one, Ringer solution was perfused in three catheters, the response to heating was measured, 2 g/l losartan, 10 mM nitro-L-arginine (NLA), or NLA ϩ losartan was added to perfusate, and the heat response was remeasured; in another, 10 M ANG II was given, the heat response was measured, losartan, NLA, or NLA ϩ losartan was added to ANG II, and the heat response was reassessed. The heat response decreased with ANG II, particularly the plateau phase (47 Ϯ 5 vs. 84 Ϯ 3 %CVC max). Losartan increased baseline conductance in both experiments (from 8 Ϯ 1 to 20 Ϯ 2 and 12 Ϯ 1 to 24 Ϯ 3). Losartan increased the ANG II response (83 Ϯ 4 vs. 91 Ϯ 6 in Ringer). NLA decreased both angiotensin and Ringer responses (31 Ϯ 4 vs. 43 Ϯ 3). NLA ϩ losartan blunted the Ringer response (48 Ϯ 2), but the ANG II response (74 Ϯ 5) increased. In a second set of experiments, we used dose responses to ANG II (0.1 nM to 10 M) with and without NLA ϩ losartan to confirm graded responses. Sodium ascorbate (10 mM) restored the ANG II-blunted heating plateau. NO synthase and AT 1R inhibition cause an NO-independent angiotensin-mediated vasodilation with local heating. ANG II mediates the AT1R blunting of local heating, which is not exclusively NO dependent, and is improved by antioxidant supplementation. lasers; conductance; skin THE VASODILATION RESPONSE of nonglabrous skin to local heating can be described in terms of distinct phases including an initial thermal peak, a decrease to a nadir, and an increase to a plateau (17,19). The plateau phase is nitric oxide (NO) dependent (17,19). It has been used to evaluate NO bioavailability (15,26,32). Recently, we observed that plasma angiotensin II (ANG II) is increased in a subset of patients with postural tachycardia syndrome (POTS) (25,27) in whom we demonstrated blunted cutaneous microvascular NO-dependent vasodilation to local heat (18). We further demonstrated that ANG II type 1 receptor (AT 1 R) blockade with losartan corrects the cutaneous NO deficit in these patients (26). This is consistent with ANG II vasoconstrictive capabilities including the ability to produce direct smooth muscle vasoconstriction (30). However, one of the most potent vasoconstrictive actions of ANG II is mediated by AT 1 R-dependent interactions with NADPH oxidase, resulting in an enhanced production of reactive oxygen species (ROS) (11-13). One such ROS is superoxide, which scavenges and combines with NO to produce peroxynitrite (21). Thus a potent oxidative/nitrative agent i...