Atrial natriuretic hormone responses to clonidine in patients with panic disorder and in healthy control subjects. Recently, Baranowska et al. (1) reported that i.v..
European Journal of Endocrinology (1997) 137 84–85
ISSN 0804-4643
LETTER TO THE EDITOR
Atrial natriuretic hormone responses to clonidine in patients with panic disorder and in healthy control subjects Recently, Baranowska et al. (1) reported that i.v. injection of 0.15 mg clonidine significantly increased plasma atrial natriuretic hormone (ANH) concentrations in normal-weighted and obese women within 15 min. Thus, they extended their preclinical findings showing that stimulation of the a-2-adrenergic receptors is a very potent signal for ANH secretion in both normally-hydrated and water-deprived rats (2, 3). Against the background of ANH hypersecretion by a panicogenic sodium lactate infusion (4) and a downregulation of the a-2 receptor function in patients with panic disorder (5), we studied the response of ANH to clonidine in these subjects and in healthy controls. Ten patients with panic disorder (according to DSMIII-R criteria (6), without comorbid current other axis I disorder and without medication for at least 14 days) (8 females, 2 males; age 3269 years) and seven healthy controls, matched for age and sex (5 females, 2 males; age 3164 years) were studied. None of the participants had been subjected to sleep deprivation, alcohol, excessive coffee intake, nicotine intake (restricted to three cigarettes on the day before investigation) or time shifts during the three months preceding the study. In addition, all subjects were also free of non-prescription drugs such as antihistamines for at least three months. Urinary drug screens were negative for each subject and at each investigation. The protocol was approved by the ethics committee for human experiments and written informed consent was given by each participant prior to the investigation. All subjects were studied in a singlebedded room in a supine position from 0800 h to 1100 h on two separate days after an overnight fast. In a randomized single-blind design they received an intravenous injection of 2 mg/kg body weight clonidine (Catapressan; Boehringer, Mannheim, Germany) in 10 ml normal saline or 10 ml normal saline as placebo at 1000 h. ANH was determined at 1000, 1005, and 1015 h radioimmunometrically (Nichols Institute, San Juan Capistrano, CA, USA) after C18 extraction. Minimum detectable amounts were 8 pg/ml. The inter- and intra-assay coefficients of variation were below 10%. Statistical evaluation was performed using a threefactorial multivariate analysis of variance with repeated measures design. Group was a between-subjects factor and treatment and time were within-subjects factors. To avoid carry-over effects, the ANH values at 1005 h and 1015 h were normed over the basal values before statistical evaluation. Basal ANH concentrations at 1000 h were significantly lower in the patients (mean6S.E.M., 7665.4 pg/ q 1997 Society of the European Journal of Endocrinology
Figure 1 ANH concentrations following clonidine (solid bars) and placebo (open bars) administration in controls and patients with panic disorder. Results are given as mean normed values6S.E.M. on the basis of the 1000 h ANH plasma concentrations.
ml) than in the controls (10367.2 pg/ml; F(1,32)=8.9; significance of F=0·005). Comparing the three time points MANOVA showed no significant main or interaction effects for ANH (see Fig. 1) heart rate and blood pressure. Circulatory parameters remained unchanged throughout the investigation and no parameter indicated any treatment effect, especially no decrease in cardiac output. In contrast to Baranowska et al. (1), no response of ANH to clonidine was seen in our experiments using a similar dosage. However, as neither the time of administration of clonidine nor the position of the subjects are described by (1), a direct comparison of the results is difficult. Interestingly, the significantly lower basal levels of ANH in panic patients further point to an alteration in ANH regulation as did the enhanced release after lactate (4). The characterization of the responses to other stimuli of the ANH system in panic patients is needed to elucidate further its role in the pathophysiology of this disorder.
Acknowledgements We thank Mrs G Gajewski for technical assistance.
References 1 Baranowska B, Wasilewska-Dziubinska E, Radzikowska M, Plonowski A & Roguski K. Impaired response of atrial natriuretic
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peptide to acute water load in obesity and in anorexia nervosa. European Journal of Endocrinology 1995 132 147–151. 2 Baranowska B, Gutkowska J, Cantin M & Genest J. Plasma immunoreactive atrial natriuretic factor (IR-ANF) increases markedly after a-2-adrenergic stimulation with clonidine in normally-hydrated rats. Biochemical and Biophysical Research Communications 1987 143 159–163. 3 Baranowska B, Tremblay J & Gutkowska J. Clonidine stimulates atrial natriuretic factor (ANF) release in water-deprived rats. Peptides 1988 9 189–192. 4 Kellner M, Herzog L, Yassouridis A, Holsboer F & Wiedemann K. Possible role of atrial natriuretic hormone in pituitary–adrenocortical unresponsiveness in lactate-induced panic. American Journal of Psychiatry 1995 152 1365–1367.
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5 Brambilla F, Perna G, Gaberi A, Nobile P & Bellodi L. Alpha-2adrenergic receptor sensitivity in panic disorder. Psychoneuroendocrinology 1994 20 1–9. 6 Spitzer RL, Williams JBW & Gibbon M. Structured Clinical Interview for DSM-III-R (SCID). New York: New York State Psychiatric Institute, Biometrics Research, 1987. Michael Kellner and Klaus Wiedemann, Max Planck Institute of Psychiatry, Clinical Institute, Department of Psychiatry, Kraepelinstrasse 10, D-80804 Munich, Germany
Received 18 November 1996 Accepted 10 March 1997
