title: Altered systemic hemodynamic and baroreflex response to angiotensin II in postural tachycardia syndrome.
abstract: BACKGROUND
  Postural tachycardia syndrome (POTS) is characterized by excessive orthostatic tachycardia and significant functional disability. We have previously found that patients with POTS have increases in plasma angiotensin II (Ang II) that are twice as high as healthy subjects despite normal blood pressures (BPs). In this study, we assess systemic and renal hemodynamic and functional responses to Ang II infusion in patients with POTS compared with healthy controls.
  
  
  RESULTS
  Following a 3-day sodium-controlled diet, we infused Ang II (3 ng/kg per minute) for 1 hour in patients with POTS (n=15) and healthy controls (n=13) in the supine position. All study subjects were women with normal BP. Ages were similar for patients with POTS and controls (mean±SEM, 30±2 versus 26±1 years; P=0.11). We measured the changes from baseline mean arterial pressure, renal plasma flow, plasma renin activity, aldosterone, urine sodium, and baroreflex sensitivity in both groups. In response to Ang II infusion, patients with POTS had a blunted increase compared with controls in mean arterial pressure (10±1 versus 14±1 mm Hg, P=0.01) and diastolic BP (9±1 versus 13±1 mm Hg, P=0.01) but not systolic BP (13±2 versus 15±2 mm Hg, P=0.40). Renal plasma flow decreased similarly with Ang II infusion in patients with POTS versus controls (-166±20 versus -181±17 mL/min per 1.73 kg/m(2), P=0.58). Postinfusion, the decrease in plasma renin activity (-0.9±0.2 versus -0.6±0.2 ng/mL per hour, P=0.43) and the increase in aldosterone (17±1 versus 15±2 pg/mL, P=0.34) were similar in both groups. The decrease in urine sodium excretion was similar in patients with POTS and controls (-49±12 versus -60±16 mEq/g creatinine, P=0.55). The spontaneous baroreflex sensitivity at baseline was significantly lower in patients with POTS compared with controls (10.1±1.2 versus 16.8±1.5 ms/mm Hg, P=0.003), and it was further reduced with Ang II infusion.
  
  
  CONCLUSIONS
  Patients with POTS have blunted vasopressor response to Ang II and impaired baroreflex function. This impaired vasoconstrictive response might be exaggerated with upright posture and may contribute to the subsequent orthostatic tachycardia that is the hallmark of this disorder. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00962949.
authors.affiliation: Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232-2195, USA.
authors.forename: Hossam I
authors.initials: HI
authors.lastname: Mustafa
authors.forename: Satish R
authors.initials: SR
authors.lastname: Raj
authors.forename: André
authors.initials: A
authors.lastname: Diedrich
authors.forename: Bonnie K
authors.initials: BK
authors.lastname: Black
authors.forename: Sachin Y
authors.initials: SY
authors.lastname: Paranjape
authors.forename: William D
authors.initials: WD
authors.lastname: Dupont
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Williams
authors.forename: Italo
authors.initials: I
authors.lastname: Biaggioni
authors.forename: David
authors.initials: D
authors.lastname: Robertson
mesh_terms: D000293:Adolescent; D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage / Q000627:therapeutic use*; D017704:Baroreflex / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D054972:Postural Orthostatic Tachycardia Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D014662:Vasoconstrictor Agents; D000804:Angiotensin II