Angiotensin-II in POTS

Home ] Up ] 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 ]

Postural tachycardia syndrome (POTS) is associated with low blood volume, reduced renin and aldosterone. Angiotensin-II has not been investigated. Past work suggested that a subset of POTS, with increased vasoconstriction related to decreased bioavailable nitric oxide, had decreased blood volume. Angiotensin-II reduces bioavailable NO and is integral to the renin-angiotensin system. Thus, we investigated the relationship among blood volume, angiotensin-II, renin, aldosterone and peripheral blood flow in POTS.

            POTS was diagnosed by 70o upright tilt. Supine calf blood flow measured by venous occlusion plethysmography was used to subgroup POTS patients. 23 POTS patients were partitioned among 10 with low blood flow, 8 with normal flow, and 5 with high flow. There were 10 healthy volunteers. Blood volume was measured by dye dilution. Biochemical measurements were performed supine.  Blood volume was decreased in low flow POTS (2.14±.12 L/M2) compared to control (2.76±.20 L/M2) but not in other subgroups. PRA was decreased in low flow POTS (0.49±.12 vs 0.90±0.18 ng/ml/hr), while plasma angiotensin-II was increased (89±20 vs 32±4 ng/L), but not in other subgroups. PRA correlated with aldosterone (r=+0.71) over all subjects. PRA correlated negatively with blood volume (r=-0.72) in normal and high flow POTS but positively (r=+0.65) in low flow POTS. PRA correlated positively with angiotensin (r=+0.76) in normal and high flow POTS but negatively (r=-.83) in low flow POTS. Blood volume was negatively correlated to angiotensin II (r=-0.66) in normal and high flow POTS, and in five low flow POTS patients. The remaining five patients had reduced blood volume and increased angiotensin-II uncorrelated to blood volume. Data suggest that plasma angiotensin-II is increased in low flow POTS patients with hypovolemia which may contribute to local blood flow dysregulation and reduced NO bioavailability.  

 


 

Table 1 Patient Dimensions and Hemodynamic Data

                           Control

POTS

 

Control

Low Flow

Normal Flow

High Flow

Body Surface Area (M2)

1.72±.04

1.73±.12

1.81±.07

1.69±.17

Weight (kg)

68±2

62±4

70±4

63±6

Height (cm)

166±2

178±9

172±3

169±7

Normalized Blood Volume

 (L/ M2)

2.76±.20

2.14±.12*

2.86±.26

3.18±.26

Hematocrit (%)

41±1

41±2

42±1

41±0.3

Supine HR (bpm)

68±3

84±4*

76±6

75±11

MAP (mmHg)

78±2

84±4

79±2

77±2

Calf Venous Pressure (mmHg)

13±1

18±1*

12±1

10±2

Calf Blood Flow (ml/100ml)

3.0±0.4

0.9±0.07*

2.6±0.2

4.9±0.3*

Calf Peripheral Resistance

(mmHg/ml/100ml/min)

30±4

61±10*

26±3

13±2*

 

The shows results for plasma renin activity (PRA) in left panel, serum aldosterone in the middle panel, and plasma angiotensin II concentration in the right panel for all subjects. PRA is significantly decreased and angiotensin is increased in low flow POTS patients compared to controls subjects. Angiotensin II concentrations seem to follow a bimodal distribution.

 

The figure shows the relation between serum aldosterone and plasma renin activity. There is a positive correlation between renin and aldosterone across all groups.

 

The shows the relation between angiotensin II radioimmunoassay results and plasma renin activity. There is a significant negative correlation between plasma angiotensin II concentration and plasma renin activity for low flow POTS (dashed line). There is a positive correlation between plasma renin activity and plasma angiotensin II concentration for normal flow and high flow POTS (solid line).

 

The figure shows the relation between blood volume and angiotensin II radioimmunoassay results. There is a significant negative correlation between blood volume and plasma angiotensin II concentration for normal flow and high flow POTS (solid line). Low flow POTS segregates into two subgroups: those with increased plasma angiotensin II concentration being at low blood volumes with little liner relation between the variables, while those with angiotensin within the usual normal range fall on the “normal flow” regression line. 

 

A subset of POTS patients are significantly hypovolemic and hypovolemia is “paradoxically” associated with hyporeninemia and hypoaldosteronemia. In the present work we link hyporeninemia to a specific subset of low flow POTS with increased plasma angiotensin II and reduced blood volume.

Blockade of AT1R by losartan reversed reduced bioavailability of nitric oxide in low flow POTS

 


Up
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