Corticosteroids and the cardiovascular response to stress: a pilot study of the 35% CO2 challenge in Addison's disease.
OBJECTIVE
Glucocorticoids play an essential role in the neuroendocrine response to stress, influencing both the hypothalamic-pituitary-adrenal (HPA) axis and the sympatho-adrenomedullary (SAM) axis at several levels. In this pilot study, a clinical model of primary adrenocortical failure (Addison's disease, AD) has been used to evaluate the role of circulating glucocorticoids in both the autonomic and psychological response to stress.


METHODS
Five subjects with known AD underwent a randomized, double-blind, placebo-controlled investigation in which they received fixed glucocorticoid plus mineralocorticoid hormone replacement or placebo for 48 h prior to a 35% CO2 challenge.


METHODS
Psychological responses immediately before and after CO2 exposure were assessed by questionnaire. Systolic blood pressure (SBP) and heart rate were measured automatically at 1-min intervals for 5 min before and 5 min after the CO2 exposure.


RESULTS
While on hormone replacement, all subjects had an identical response to CO2 to that recorded in normal volunteers (initial bradycardia, an increase in blood pressure and subjective feelings of anxiety). On no replacement, however, the bradycardia and anxiety responses were not significantly altered, but the pressor response was markedly attenuated (+15.6 +/- 5 mmHg on replacement compared with +4.2 +/- 3.3 mmHg off replacement; P = 0.043).


CONCLUSIONS
These data provide further evidence that the CO2-induced bradycardia is a direct--presumably parasympathetic--response to CO2 independent of the pressor effect, and that the pressor response itself is dependent on the presence of the circulating corticosteroid.
Kaye
J M
JM
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Bristol, UK. joey.kaye@health.wa.gov.au
Lightman
S L
SL
D000224:Addison Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D001007:Anxiety; D001143:Arousal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005438:Fludrocortisone / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D018709:Statistics, Nonparametric; D013315:Stress, Psychological
D000305:Adrenal Cortex Hormones; D002245:Carbon Dioxide; D005438:Fludrocortisone; D006854:Hydrocortisone