Opposite to alpha2-adrenergic agonists, an imidazoline I1 selective compound does not influence reflex bradycardia in rabbits.
This work aimed to study the respective effects of central alpha2-adrenergic receptors (alpha2-ARS) and I1 imidazoline receptors (I1Rs) 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 I1Rs, 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 microg/kg, i.c.), a hybrid ligand which binds to both I1 and alpha2-ARS, 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 microg/kg, i.c.), a ligand selective for alpha2-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 I1Rs which decreases arterial pressure, does not potentiate the RB ii) activation of alpha2-ARs potentiates the RB (iii) the R-R prolongation caused by alpha2-ARs stimulation is prevented by central NOS inhibition.
Sy
Guata Yoro
GY
Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, INSERM U 715, Faculté de Médecine, Université Louis Pasteur, 11 rue Humann, 67000 Strasbourg, France.
Bousquet
Pascal
P
Feldman
Josiane
J
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000502:physiology; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia / Q000139:chemically induced* / Q000503:physiopathology; D001933:Brain Stem / Q000187:drug effects* / Q000502:physiology; D003521:Cyclopropanes / Q000494:pharmacology; D020927:Dexmedetomidine / Q000494:pharmacology; D004347:Drug Interactions / Q000502:physiology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D054755:Imidazoline Receptors; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D011955:Receptors, Drug / Q000819:agonists* / Q000378:metabolism; D012154:Reticular Formation / Q000187:drug effects / Q000502:physiology; D000077769:Rilmenidine; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D003521:Cyclopropanes; D004791:Enzyme Inhibitors; D054755:Imidazoline Receptors; C427228:LNP 509; D010080:Oxazoles; D011758:Pyrroles; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; C487767:imidazoline receptor 2; D010656:Phenylephrine; D009569:Nitric Oxide; D020927:Dexmedetomidine; D019001:Nitric Oxide Synthase; D000077769:Rilmenidine