Anxiolyticlike Effects of Atrial Natriuretic Peptide on Cholecystokinin Tetrapeptide–Induced Panic Attacks: Preliminary Findings | Anxiety Disorders | JAMA Psychiatry | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 35.170.64.36. Please contact the publisher to request reinstatement.
1.
Gorman  JMBattista  DGoetz  RRDillon  DJLiebowitz  MRFyer  AJKahn  JPSandberg  DKlein  DF A comparison of sodium bicarbonate and sodium lactate infusion in the induction of panic attacks.  Arch Gen Psychiatry. 1989;46145- 150Google ScholarCrossref
2.
Klein  DF False suffocation alarms, spontaneous panics, and related conditions: an integrative hypothesis.  Arch Gen Psychiatry. 1993;50306- 317Google ScholarCrossref
3.
Nutt  DJLawson  CW Panic attacks: a neurochemical overview of models and mechanisms.  Br J Psychiatry. 1992;160165- 178Google ScholarCrossref
4.
Curtis  ALLechner  SMPavcovich  LAValentino  RJ Activation of the locus coeruleus noradrenergic system by intracoerulear microinfusion of corticotropin-releasing factor: effects on discharge rate, cortical norepinephrine levels and cortical electroencephalographic activity.  J Pharmacol Exp Ther. 1997;281163- 172Google Scholar
5.
Butler  PDWeiss  JMStout  JCNemeroff  CB Corticotropin-releasing factor produces fear-enhancing and behavioral activating effects following infusion into the locus coeruleus.  J Neurosci. 1990;10176- 180Google Scholar
6.
Biró  EGardi  JVecsernyés  MJulesz  JTóth  GTelegdy  G The effects of atrial natriuretic peptide (ANP1-28) on corticotropin releasing factor in brain of rats.  Life Sci. 1996;591351- 1356Google ScholarCrossref
7.
Skutella  TProbst  JCRenner  UHolsboer  FBehl  C Corticotropin-releasing hormone receptor (type I) antisense targeting reduces anxiety.  Neuroscience. 1998;85795- 805Google ScholarCrossref
8.
Timpl  PSpanagel  RSillaber  IKresse  AReul  JMHMStalla  GKBlanquet  VSteckler  THolsboer  FWurst  W Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1.  Nat Genet. 1998;19162- 166Google ScholarCrossref
9.
Holsboer  Fvon Bardeleben  UBuller  RHeuser  ISteiger  A Stimulation response to corticotropin-releasing hormone (CRH) in patients with depression, alcoholism and panic disorder.  Horm Metab Res Suppl. 1987;1680- 88Google Scholar
10.
Liebowitz  MLGorman  JMFyer  AJLevitt  MDillon  DLevy  GAppleby  ILAnderson  SPalij  MDavies  SOKlein  DF Lactate provocation of panic attacks, II: biochemical and physiological findings.  Arch Gen Psychiatry. 1985;42709- 719Google ScholarCrossref
11.
Kellner  MHerzog  LYassouridis  AHolsboer  FWiedemann  K Possible role of atrial natriuretic hormone in pituitary-adrenocortical unresponsiveness in lactate-induced panic.  Am J Psychiatry. 1995;1521365- 1367Google Scholar
12.
Kellner  MWiedemann  K Nonresponse of adrenocorticotropic hormone in first-ever lactate-induced panic attacks in healthy volunteers.  Arch Gen Psychiatry. 1998;5585- 86Google ScholarCrossref
13.
Jessop  DS Central non-glucocorticoid inhibitors of the hypothalamo-pituitary-adrenal axis.  J Endocrinol. 1999;160169- 180Google ScholarCrossref
14.
Kellner  MWiedemann  KHolsboer  F Atrial natriuretic factor inhibits the CRH-stimulated secretion of ACTH and cortisol in man.  Life Sci. 1992;501835- 1842Google ScholarCrossref
15.
Kellner  MKnaudt  KJahn  HHolsboer  FWiedemann  K Atrial natriuretic hormone in lactate-induced panic attacks: mode of release and endocrine and pathophysiological consequences.  J Psychiatr Res. 1998;3237- 48Google ScholarCrossref
16.
Seier  FEKellner  MYassouridis  AHeese  RStrian  FWiedemann  K Autonomic reactivity and hormonal secretion in lactate-induced panic attacks.  Am J Physiol. 1997;272H2630- H2638Google Scholar
17.
Ströhle  AJahn  HMontkowski  ALiebsch  GBoll  ELandgraf  RHolsboer  FWiedemann  K Central and peripheral administration of atriopeptin is anxiolytic in rats.  Neuroendocrinology. 1997;65210- 215Google ScholarCrossref
18.
Wiedemann  KJahn  HKellner  M Effects of natriuretic peptides upon hypothalamo-pituitary-adrenocortical system activity and anxiety behaviour.  Exp Clin Endocrinol Diabetes. 2000;1085- 13Google Scholar
19.
Bradwejn  JKoszycki  DMeteressian  G Cholecystokinin-tetrapeptide induces panic attacks in patients with panic disorder.  Can J Psychiatry. 1990;3583- 85Google Scholar
20.
Kellner  MYassouridis  AJahn  HWiedemann  K Influence of clonidine on psychopathological, endocrine and respiratory effects of cholecystokinin tetrapeptide in patients with panic disorder.  Psychopharmacology. 1997;13355- 61Google ScholarCrossref
21.
Shlik  JAluoja  AVasar  VVasar  EPodar  TBradwejn  J Effects of citalopram on behavioral, cardiovascular and neuroendocrine response to cholecystokinin tetrapeptide challenge in patients with panic disorder.  J Psychiatry Neurosci. 1997;22332- 340Google Scholar
22.
Wittchen  HUZaudig  MSchramm  ESpengler  PMombour  WKlug  JHorn  R SKID: Strukturiertes klinisches Interview für DSM-III-R.  Weinheim, Germany Beltz1991;
23.
Dillon  DGorman  JMLiebowitz  MRFyer  AJKlein  DF The measurement of lactate-induced panic anxiety.  Psychiatry Res. 1987;2097- 105Google ScholarCrossref
24.
Hiller  Wvon Bose  MDichtl  GAgerer  D Reliability of checklist-guided diagnoses for DSM-III-R affective and anxiety disorders.  J Affect Disord. 1990;20235- 247Google ScholarCrossref
25.
Bradwejn  JKoszycki  SShriqui  C Enhanced sensitivity to cholecystokinin-tetrapeptide in panic disorder.  Arch Gen Psychiatry. 1991;48603- 610Google ScholarCrossref
26.
Wank  SA Cholecystokinin receptors.  Am J Physiol. 1995;269G628- G646Google Scholar
27.
LeMellédo  J-MBradwejn  JKoszycki  DBichet  DGBellavance  F The role of the β-noradrenergic system in cholecystokinin-tetrapeptide–induced panic symptoms.  Biol Psychiatry. 1998;44364- 366Google ScholarCrossref
28.
Langub  MCWatson  REHerman  JP Distribution of natriuretic peptide precursor mRNAs in the rat brain.  J Comp Neurol. 1995;356183- 199Google ScholarCrossref
29.
Yoshimura  TYoshimura  MYasue  HIto  MOkamura  HMukoyama  MNakao  K Plasma concentrations of atrial natriuretic peptide and brain natriuretic peptide during normal human pregnancy and the postpartum period.  J Endocrinol. 1994;140393- 397Google ScholarCrossref
30.
Northcott  EJStein  MB Panic disorder in pregnancy.  J Clin Psychiatry. 1994;55539- 542Google Scholar
31.
Bidzseranova  AGueron  JToth  GPenke  BVarga  JTeledgy  G Behavioral effects of atrial natriuretic and brain natriuretic peptides in rats.  Neuroreport. 1992;3283- 285Google ScholarCrossref
32.
Holsboer  Fvon Bardeleben  USteiger  A Effects of intravenous corticotropin-releasing hormone upon sleep-related growth hormone surge and sleep EEG in man.  Neuroendocrinology. 1988;4832- 38Google ScholarCrossref
33.
Banks  WAKastin  AJ Differential permeability of the blood-brain barrier to two pancreatic peptides: insulin and amylin.  Peptides. 1998;19883- 889Google ScholarCrossref
34.
Kamilaris  TCJohnson  EOCalogero  AEKalogeras  KTBernardini  RChrousos  GPGold  PW Cholecystokinin-octapeptide stimulates hypothalamic-pituitary-adrenal function in rats: role of corticotropin-releasing hormone.  Endocrinology. 1992;1301764- 1774Google Scholar
35.
Atchison  DJAckermann  U The interaction between atrial natriuretic peptide and cardiac parasympathetic function.  J Auton Nerv Syst. 1993;4281- 88Google ScholarCrossref
36.
Cameron  OGLee  MACurtiss  GCMcCann  DS Endocrine and physiological changes during "spontaneous" panic attacks.  Psychoneuroendocrinology. 1987;12321- 331Google ScholarCrossref
37.
Curtis  GBuxton  MLippmann  DNesse  RWrigth  J "Flooding in vivo" during the circadian phase of minimal cortisol secretion: anxiety and therapeutic success without adrenal cortical activation.  Biol Psychiatry. 1976;11101- 107Google Scholar
38.
Bierwolf  CBurgemeister  ALuthke  KBorn  JFehm  HL Influence of exogenous atrial natriuretic peptide on the pituitary-adrenal response to corticotropin-releasing hormone and vasopressin in healthy men.  J Clin Endocrinol Metab. 1998;831151- 1157Google ScholarCrossref
39.
Franci  CRAnselmo-Franci  JFMcCann  SM The role of endogenous atrial natriuretic peptide in resting and stress-induced release of corticotropin, prolactin, growth hormone, and thyroid-stimulating hormone.  Proc Natl Acad Sci U S A. 1992;8911391- 11395Google ScholarCrossref
40.
Arborelius  LOwens  MJPlotsky  PMNemeroff  CB The role of corticotropin-releasing factor in depression and anxiety disorders.  J Endocrinol. 1999;1601- 12Google ScholarCrossref
41.
Kellner  MYehuda  R Do panic disorder and posttraumatic stress disorder share a common psychoneuroendocrinology?  Psychoneuroendocrinology. 1999;24485- 504Google ScholarCrossref
42.
Lim  ATSheward  WJCopolov  DWindmill  DFink  G Atrial natriuretic factor is released into hypophysial portal blood: direct evidence that atrial natriuretic factor may be a neurohormone involved in hypothalamic pituitary control.  J Neuroendocrinol. 1990;215- 17Google ScholarCrossref
43.
Colao  APivonello  RFerone  DFaggiano  AFacciolli  GDi Somma  CBoudouresque  FOliver  CLombardi  G Effect of corticotrophin-releasing hormone on arginine vasopressin and atrial natriuretic factor in patients with Cushing's disease.  Clin Endocrinol (Oxf). 1998;4977- 84Google ScholarCrossref
44.
Yeragani  VKSrinivasan  KBalon  RRamesh  CBerchou  R Lactate sensitivity and cardiac cholinergic function in panic disorder.  Am J Psychiatry. 1994;1511226- 1228Google Scholar
45.
Yeragani  VKSrinivasan  KPohl  RBerger  RBalon  RBerchou  R Sodium lactate increases sympathovagal ratios in normal control subjects: spectral analysis of heart rate, blood pressure, and respiration.  Psychiatry Res. 1994;5497- 114Google ScholarCrossref
46.
George  DTNutt  DJWalker  WVPorges  SWAdinoff  BLinnoila  M Lactate and hyperventilation substantially attenuate vagal tone in normal volunteers.  Arch Gen Psychiatry. 1989;46153- 156Google ScholarCrossref
47.
Butler  GCBeverley  LSFloras  JS Influence of atrial natriuretic factor on heart rate variability in normal men.  Am J Physiol. 1994;267H500- H505Google Scholar
48.
Pettersson  ARicksten  SETowle  ACHedner  JHedner  T Effect of blood volume expansion and sympathetic denervation on plasma levels of atrial natriuretic factor (ANF) in the rat.  Acta Physiol Scand. 1985;124309- 311Google ScholarCrossref
49.
Jiao  JHBaertschi  AJ Neural control of the endocrine heart.  Proc Natl Acad Sci U S A. 1993;907799- 7803Google ScholarCrossref
50.
McKitrick  DJCalaresu  FR Cardiovascular responses to microinjection of ANF into dorsal medulla of rats.  Am J Physiol. 1988;255R182- R187Google Scholar
51.
Schultz  HDSteele  MKGardner  DG Central administration of atrial natriuretic peptide decreases sympathetic outflow in rats.  Am J Physiol. 1990;258R1250- R1256Google Scholar
52.
Geiger  HBahner  UPalkovits  MHeidland  ASterzel  RB Atrial natriuretic peptide in the locus coeruleus and its possible role in the regulation of arterial blood pressure, fluid and electrolyte homeostasis.  Life Sci. 1991;49869- 879Google ScholarCrossref
Original Article
April 2001

Anxiolyticlike Effects of Atrial Natriuretic Peptide on Cholecystokinin Tetrapeptide–Induced Panic Attacks: Preliminary Findings

Author Affiliations

From the Department of Psychiatry and Psychotherapy, University of Hamburg, Hamburg (Drs Wiedemann, Jahn, and Kellner), and Max Planck Institute of Psychiatry, Munich (Drs Wiedemann, Yassouridis, and Kellner), Germany.

Arch Gen Psychiatry. 2001;58(4):371-377. doi:10.1001/archpsyc.58.4.371
Abstract

Background  Panic attacks induced by administration of cholecystokinin tetrapeptide (CCK-4) have been evaluated as a valuable tool to investigate the neurobiological mechanisms involved in panic anxiety. The rationale to study the effects of natriuretic peptides on the CCK-4 response is derived from observations that atrial natriuretic peptide (ANP) is released during panic attacks in humans and has anxiolyticlike actions in various animal models.

Methods  A double-blind, placebo-controlled design was conducted in 9 patients with panic disorder and 9 similar healthy control subjects. After pretreatment with an infusion of 150 µg of ANP or placebo in random order, each subject received 50 µg of CCK-4. Psychopathological parameters as well as physiological measures were sampled before and after CCK-4 administration.

Results  After pretreatment with ANP, the number of CCK-4–induced panic attacks decreased from 8 to 6 in patients and from 5 to 2 in controls. Acute Panic Inventory ratings were significantly reduced in patients after ANP vs placebo pretreatment. Infusion of ANP significantly curtailed the CCK-4–induced release of corticotropin in patients. Heart rate variability analysis indicated a sympathetic stimulation by CCK-4 that was inhibited by ANP in patients and controls.

Conclusions  The present study indicates that ANP exerts anxiolyticlike effects on CCK-4–stimulated anxiety attacks in patients with panic disorder. In addition, ANP produced an inhibition of the hypothalamopituitary-adrenocortical system and sympatholytic effects.

×