Abnormalities of angiotensin regulation in postural tachycardia syndrome.
BACKGROUND
Postural tachycardia syndrome (POTS) is a disorder characterized by excessive orthostatic tachycardia and significant functional disability. We previously reported that POTS patients have low blood volume and inappropriately low plasma renin activity (PRA) and aldosterone. In this study, we sought to more fully characterize the renin-angiotensin-aldosterone system (RAAS) to gain a better understanding of the pathophysiology of POTS.


OBJECTIVE
The purpose of this study was to prospectively assess the plasma levels of angiotensin (Ang) peptides and their relationship to other RAAS components in patients with POTS compared with healthy controls.


METHODS
Heart rate, PRA, Ang I, Ang II, Ang (1-7), and aldosterone were measured in POTS patients (n = 38) and healthy controls (n = 13) while they were consuming a sodium-controlled diet.


RESULTS
POTS patients had larger orthostatic increases in heart rate than did controls (52 ± 3 [mean ± SEM] bpm vs 27 ± 6 bpm, P = .001). Plasma Ang II was significantly higher in POTS patients (43 ± 3 pg/mL vs 28 ± 3 pg/mL, P = .006), whereas plasma Ang I and angiotensin 1-7 [Ang-(1-7)] were similar between groups. Despite the twofold increase of Ang II, POTS patients trended to lower PRA levels than did controls (0.9 ± 0.1 ng/mL/h vs 1.6 ± 0.5 ng/mL/h, P = .268) and lower aldosterone levels (4.6 ± 0.8 pg/mL vs 10.0 ± 3.0 pg/mL, P = .111). Estimated angiotensin-converting enzyme-2 (ACE2) activity was significantly lower in POTS patients than in controls (0.25 ± 0.02 vs 0.33 ± 0.03, P = .038).


CONCLUSIONS
Some patients with POTS have inappropriately high plasma Ang II levels, with low estimated ACE2 activity. We propose that these abnormalities in Ang regulation may play a key role in the pathophysiology of POTS in some patients.
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2195, USA.
Hossam I
HI
Mustafa
Emily M
EM
Garland
Italo
I
Biaggioni
Bonnie K
BK
Black
William D
WD
Dupont
David
D
Robertson
Satish R
SR
Raj
D000328:Adult; D000804:Angiotensin II / Q000097:blood*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008597:Menstrual Cycle / Q000502:physiology; D054972:Postural Orthostatic Tachycardia Syndrome / Q000097:blood* / Q000503:physiopathology*; D011446:Prospective Studies; D012084:Renin-Angiotensin System / Q000502:physiology*
D000804:Angiotensin II
Circulation. 1997 Jul 15;96(2):575-80
9244228
J Am Coll Cardiol. 2008 Aug 26;52(9):750-4
18718423
Peptides. 1994;15(5):919-26
7984514
Peptides. 1991 Sep-Oct;12(5):1135-41
1666184
Health Psychol. 2003 Nov;22(6):643-8
14640863
Neurology. 1993 Jan;43(1):132-7
8423877
Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H3012-9
11087259
Circulation. 2009 Sep 1;120(9):725-34
19687359
Hypertension. 2002 Sep;40(3):348-54
12215478
Circ Res. 2010 Feb 5;106(2):373-82
19926873
Mol Pharmacol. 1995 Oct;48(4):601-9
7476884
Mayo Clin Proc. 2007 Mar;82(3):308-13
17352367
J Clin Invest. 1964 Apr;43:659-69
14149919
Clin Sci (Lond). 2006 Feb;110(2):255-63
16262605
Biochem Pharmacol. 2008 Feb 15;75(4):781-6
17897633
Indian Pacing Electrophysiol J. 2006 Apr 01;6(2):84-99
16943900
Control Clin Trials. 1990 Apr;11(2):116-28
2161310
Endocrinology. 1997 Sep;138(9):3828-35
9275071
Nature. 2002 Jun 20;417(6891):822-8
12075344
Am J Physiol Heart Circ Physiol. 2005 Sep;289(3):H1226-33
15863453
Neurology. 2007 Aug 21;69(8):790-8
17709712
J Clin Invest. 1979 Nov;64(5):1270-6
500810
Am J Med Sci. 2007 Jul;334(1):57-60
17630594
Am J Med Sci. 1999 Feb;317(2):75-7
10037110
J Biol Chem. 1997 Dec 19;272(51):32482-8
9405459
Trends Endocrinol Metab. 2004 May-Jun;15(4):166-9
15109615
Circulation. 2008 Jul 15;118(3):e61-2
18625897
Curr Hypertens Rep. 2008 Oct;10(5):410-4
18775121
N Engl J Med. 2000 Oct 5;343(14):1008-14
11018167
Circulation. 2005 Apr 5;111(13):1574-82
15781744
Hypertension. 1991 Feb;17(2):131-8
1846840
Hypertension. 1995 Apr;25(4 Pt 2):796-802
7536715
J Clin Invest. 1988 Jan;81(1):213-20
3335637
Hypertension. 2009 May;53(5):767-74
19289653