RATIONALE: It has been postulated that cardiovascular reactivity to mental stress varies with tonic central sympathetic nervous system activity, but pharmacological evidence is missing. OBJECTIVE: To test whether modulation of central sympathetic nervous system activity by alpha2-adrenergic agonism and antagonism affects cardiovascular reactivity to mental stress. MATERIALS AND METHODS: On three five-stepped dose/concentration-response study days, 12 healthy male volunteers received intravenous infusions of dexmedetomidine (alpha2-agonist, target plasma concentrations: 0.04-0.32 ng/ml), yohimbine (alpha2-antagonist, doses: 0.016-0.125 mg/kg), and placebo, respectively. During each dose step, subjects performed a 5-Choice Reaction Time Task (CRTT) and a Paced Auditory Serial Addition Task (PASAT) to induce moderate mental stress. Prestress baseline, as well as stress-induced responses of heart rate, and noninvasive finger arterial blood pressure (Finapres) were assessed. RESULTS:Prestress baseline heart rate and blood pressure decreased with increasing doses of dexmedetomidine and increased with increasing doses of yohimbine. However, dexmedetomidine and yohimbine did not affect stress-induced heart-rate and blood-pressure changes. CONCLUSIONS: Cardiovascular reactivity to mental stress is not related to pharmacologically manipulated tonic central sympathetic nervous system activity by alpha2-adrenergic agonists and antagonists. These results do not support the assumption that cardiovascular reactivity is an index of tonic central sympathetic nervous system activity.
RCT Entities:
RATIONALE: It has been postulated that cardiovascular reactivity to mental stress varies with tonic central sympathetic nervous system activity, but pharmacological evidence is missing. OBJECTIVE: To test whether modulation of central sympathetic nervous system activity by alpha2-adrenergic agonism and antagonism affects cardiovascular reactivity to mental stress. MATERIALS AND METHODS: On three five-stepped dose/concentration-response study days, 12 healthy male volunteers received intravenous infusions of dexmedetomidine (alpha2-agonist, target plasma concentrations: 0.04-0.32 ng/ml), yohimbine (alpha2-antagonist, doses: 0.016-0.125 mg/kg), and placebo, respectively. During each dose step, subjects performed a 5-Choice Reaction Time Task (CRTT) and a Paced Auditory Serial Addition Task (PASAT) to induce moderate mental stress. Prestress baseline, as well as stress-induced responses of heart rate, and noninvasive finger arterial blood pressure (Finapres) were assessed. RESULTS: Prestress baseline heart rate and blood pressure decreased with increasing doses of dexmedetomidine and increased with increasing doses of yohimbine. However, dexmedetomidine and yohimbine did not affect stress-induced heart-rate and blood-pressure changes. CONCLUSIONS: Cardiovascular reactivity to mental stress is not related to pharmacologically manipulated tonic central sympathetic nervous system activity by alpha2-adrenergic agonists and antagonists. These results do not support the assumption that cardiovascular reactivity is an index of tonic central sympathetic nervous system activity.
Authors: Jani Penttilä; Antti Helminen; Markku Anttila; Susanna Hinkka; Harry Scheinin Journal: Can J Physiol Pharmacol Date: 2004-05 Impact factor: 2.273