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Keywords:

  • Norepinephrine;
  • Clonidine;
  • Rilmenidine;
  • α-Methylnorepinephrine;
  • Electrochemistry;
  • Rostral Ventrolateral Medulla;
  • Imidazoline (I1) Receptor

Background: Enhancement of the rostral ventrolateral medulla (RVLM) presympathetic (norepinephrine, NE) neuronal activity represents a neurochemical mechanism for the pressor effect of ethanol. In this study, we tested the hypothesis that ethanol action on RVLM presympathetic neurons is selectively influenced by the signaling of the local imidazoline (I1) receptor. To support a neuroanatomical and an I1-signaling selectivity of ethanol, and to circumvent the confounding effects of anesthesia, the dose-related neurochemical and blood pressure effects of ethanol were investigated in the presence of selective pharmacological interventions that cause reduction in the activity of RVLM or nucleus tractus solitarius (NTS) NE neurons via local activation of the I1 or the α2-adrenergic receptor in conscious spontaneously hypertensive rats.

Results: Local activation of the I1 receptor by rilmenidine (40 nmol) or by the I1/α2 receptor mixed agonist clonidine (1 nmol), and local activation of the α2-adrenergic receptor (α2AR) by the pure α2AR agonist α-methylnorepinephrine (α-MNE, 10 nmol) caused reductions in RVLM NE, and blood pressure. Intra-RVLM ethanol (1, 5, or 10 μg), microinjected at the nadir of the neurochemical and hypotensive responses, elicited dose-dependent increments in RVLM NE and blood pressure in the presence of local I1—but not α2-receptor activation. Only intra-NTS α-MNE, but not rilmenidine or clonidine, elicited reductions in local NE and blood pressure; ethanol failed to elicit any neurochemical or blood pressure responses in the presence of local activation of the α2AR within the NTS.

Conclusion: The findings support the neuroanatomical selectivity of ethanol, and support the hypothesis that the neurochemical (RVLM NE), and the subsequent cardiovascular, effects of ethanol are selectively modulated by I1 receptor signaling in the RVLM.