Opposite to α 2-adrenergic agonists, an imidazoline I 1 selective compound does not influence reflex bradycardia in rabbits

Abstract

This work aimed to study the respective effects of central α 2-adrenergic receptors (α 2-AR S) and I 1 imidazoline receptors (I 1Rs) in the facilitatory effects of imidazoline-like drugs on the reflex bradycardia (RB). Experiments were performed in anaesthetized rabbits. The reflex bradycardic response was induced by phenylephrine injected i.v. LNP 509, rilmenidine and dexmedetomidine were administered intracisternally (i.c.). LNP509 (1 mg/kg, i.c.), a ligand highly selective for I 1Rs, induced hypotension (54 ± 3 vs. 93 ± 2 mm Hg) and bradycardia (260 ± 13 vs. 322 ± 13 beats/min) ( p < 0.05, n = 5) but did not affect RB. Rilmenidine (1 μg/kg, i.c.), a hybrid ligand which binds to both I 1 and α 2-AR S, also decreased arterial pressure (61 ± 2 vs. 101 ± 2 mm Hg) and heart rate (260 ± 4 vs. 308 ± 8) ( p < 0.01, n = 5); it potentiated the RB (maximum R–R interval: 284 ± 17 vs. 196 ± 6 ms) ( p < 0.05, n = 5). Dexmedetomidine (1 μg/kg, i.c.), a ligand selective for α 2-ARs, reduced blood pressure (53 ± 3 vs. 104 ± 2 mm Hg) and heart rate (246 ± 4 vs. 312 ± 8 beats/min) ( p < 0.05, n = 5) and potentiated the RB (maximum R–R interval: 518 ± 38 vs. 194 ± 4 ms) ( p < 0.05, n = 5). The potentiation of RB was much greater than that observed with rilmenidine and was significantly prevented by L-NNA injected centrally. This study shows that: (i) an exclusive action on I 1Rs which decreases arterial pressure, does not potentiate the RB ii) activation of α 2-ARs potentiates the RB (iii) the R–R prolongation caused by α 2-ARs stimulation is prevented by central NOS inhibition.