Effect of dexmedetomidine on cardiorespiratory regulation in spontaneously breathing adult rats

PURPOSE: We examined the cardiorespiratory effect of dexmedetomidine, an α(2)- adrenoceptor/imidazoline 1 (I(1)) receptor agonist, in spontaneously breathing adult rats. METHODS: Male rats (226−301 g, n = 49) under isoflurane anesthesia had their tail vein cannulated for drug administration and their tail artery cannulated for analysis of mean arterial pressure (MAP), pulse rate (PR), and arterial blood gases (PaO(2), PaCO(2), pH). After recovery, one set of rats received normal saline for control recording and was then divided into three experimental groups, two receiving dexmedetomidine (5 or 50 μg·kg(−1)) and one receiving normal saline (n = 7 per group). Another set of rats was divided into four groups receiving dexmedetomidine (50 μg·kg(−1)) followed 5 min later by 0.5 or 1 mg∙kg(−1) atipamezole (selective α(2)-adrenoceptor antagonist) or efaroxan (α(2)-adrenoceptor/I(1) receptor antagonist) (n = 6 or 8 per group). Recordings were performed 15 min after normal saline or dexmedetomidine administration. RESULTS: Compared with normal saline, dexmedetomidine (5 and 50 μg·kg(−1)) decreased respiratory frequency (f(R), p = 0.04 and < 0.01, respectively), PR (both p < 0.01), and PaO(2) (p = 0.04 and < 0.01), and increased tidal volume (both p = 0.049). Dexmedetomidine at 5 μg·kg(−1) did not significantly change minute ventilation (V′(E)) (p = 0.87) or MAP (p = 0.24), whereas dexmedetomidine at 50 μg·kg(−1) significantly decreased V′(E) (p = 0.03) and increased MAP (p < 0.01). Only dexmedetomidine at 50 μg·kg(−1) increased PaCO(2) (p < 0.01). Dexmedetomidine (5 and 50 μg·kg(−1)) significantly increased blood glucose (p < 0.01), and dexmedetomidine at 50 μg·kg(−1) increased hemoglobin (p = 0.04). Supplemental atipamezole or efaroxan administration similarly prevented the 50 μg·kg(−1) dexmedetomidine-related cardiorespiratory changes. PRINCIPAL CONCLUSION: These results suggest that dexmedetomidine-related hypoventilation and hypertension are observed simultaneously and occur predominantly through activation of α(2)-adrenoceptors, but not I(1) receptors, in spontaneously breathing adult rats.