PubMed · 9196836
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T Kamibayashi, K Harasawa, M Maze. 1997. Alpha-2 adrenergic agonists.. https://doi.org/10.1007/bf03022261
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OBJECTIVES: To determine whether the hypotensive and sympathetic baroreflex inhibition by rilmenidine administered systemically are mediated via imidazoline receptors in the rostral ventrolateral medulla (RVLM). METHODS: Initial dose-response curves to rilmenidine were determined in urethane anaesthetized rabbits. Effects of a single intravenous dose of rilmenidine (445 microg/kg) on the renal sympathetic nerve activity (RSNA) baroreflex were examined before and after microinjection into the RVLM of the mixed imidazoline/alpha2-adrenoceptor antagonist idazoxan and the alpha2-adrenoceptor antagonist 2-methoxyidazoxan (2-MI). RESULTS: Intravenous administration of rilmenidine lowered mean arterial pressure and RSNA, inhibited the RSNA baroreflex range by 33% and shifted the baroreflex curve to the left. Idazoxan injected into the RVLM reversed the hypotension and completely restored the baroreflex curve at doses that did not affect the hypotension produced by the selective alpha2-adrenoceptor agonist alpha-methylnoradrenaline. The alpha2-adrenoceptor antagonist, 2-MI also reversed the rilmenidine sympatho-inhibition suggesting that alpha2-adrenoceptors are activated as well. CONCLUSIONS: The results of the present study show that the hypotensive and sympatho-inhibitory actions of systemic rilmenidine are primarily mediated via imidazoline receptors in the RVLM. However, alpha2-adrenoceptors are also involved, probably as a direct result of the imidazoline receptor action.
The ganglionic blocking agent trimethaphan (TMP) is no longer produced. Therefore, a need exists for alternative pharmacological approaches to investigate baroreflex control of the circulation. The aim of the present study was to examine baroreflex-mediated cardiovascular responses during the administration of a muscarinic receptor antagonist (glycopyrrolate; GLY: ) and a selective alpha-2 receptor agonist (dexmedetomidine; DEX: ) and to compare responses to ganglionic blockade with TMP. We hypothesized that combined GLY-: DEX: would inhibit the baroreflex similar to TMP. Ten volunteers participated in two study days and were instrumented with pulse oximeter, nasal cannula, ECG, continuous blood pressure monitoring (Finapres), and I.V. catheter for drug infusions. Each study day consisted of a control condition followed by either combined GLY: -DEX: or TMP on alternating days. A Valsalva maneuver was performed under each condition with every subject and six subjects received bolus phenylephrine (25 mug) during GLY: -DEX: and TMP. Combined GLY: -DEX: increased (P < 0.05) blood pressure (99 +/- 4 mmHg) and heart rate (99 +/- 3 bpm) relative to control condition (BP: 90 +/- 2 mmHg; HR: 64 +/- 3 bpm) and TMP infusion decreased (P < 0.05) blood pressure (79 +/- 3 mmHg) while increasing heart rate (88 +/- 3 bpm). Valsalva maneuver elicited a persistent drop in arterial pressure (no phase IIb recovery) with the absence of a phase IV overshoot during both GLY: -DEX: and TMP conditions. Phenylephrine increased systolic pressure 34 +/- 4 mmHg under GLY: -DEX: and 23 +/- 3 mmHg with TMP (P < 0.05). Heart rate only decreased 1 +/- 2 bpm during GLY: -DEX: and 1 +/- 1 bpm with TMP. Taken together, our results suggest that GLY: -DEX: is a reasonable alternative to TMP for baroreflex inhibition.
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.