Involvement of imidazoline receptors in the baroreflex effects of rilmenidine in conscious rabbits.
OBJECTIVE
It has been suggested that imidazoline receptors rather than alpha2-adrenoceptors are involved in the sympathoinhibitory action of centrally acting antihypertensive drugs such as rilmenidine. In the present study, we examined the relative importance of alpha2-adrenoceptors and imidazoline receptors in modulating the renal sympathetic and heart rate (HR) baroreflex in response to central administration of rilmenidine in conscious normotensive rabbits.


METHODS
In seven conscious rabbits, chronically instrumented with a fourth ventricular (4V) catheter, aortic and vena caval cuff occluders and a renal nerve electrode, we continuously recorded renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and HR and assessed baroreflex MAP-RSNA and MAP-HR relationships with balloon-induced ramp rises and falls in MAP. Rabbits were treated with 4V rilmenidine (22 microg/kg) followed by 4V idazoxan (30 microg/kg; a mixed alpha2-adrenoceptor and imidazoline receptor antagonist) or 4V 2-methoxy-idazoxan (1 microg/kg; an alpha2-adrenoceptor antagonist with little affinity for imidazoline receptors).


RESULTS
Rilmenidine lowered blood pressure by 24% and reduced both upper and lower plateaus of the renal sympathetic baroreflex curve, such that the RSNA range (difference between plateaus) was reduced by 40% (-32 +/- 10 normalized units). Curves were shifted to the left with the fall in MAP. Idazoxan restored MAP, maximum RSNA and the RSNA baroreflex range. By contrast the alpha2-adrenoceptor antagonist 2-methoxy-idazoxan caused only a partial recovery of MAP and RSNA baroreflex upper plateau and range (-9 +/- 2 mmHg, 29 and 33% lower than control). Both antagonists partially restored the HR baroreflex.


CONCLUSIONS
These findings suggest that in conscious rabbits, both imidazoline receptors and alpha2-adrenoceptors are involved in the central antihypertensive and baroreflex actions of rilmenidine, but that activation of imidazoline receptors is more important for its renal sympathoinhibitory action.
Head
G A
GA
Neuropharmacology Laboratory, Baker Medical Research Institute, PO Box 6492 Melbourne, Victoria 8008, Australia. Geoff.Head@baker.edu.au
Burke
S L
SL
Sannajust
F J
FJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D020546:Fourth Ventricle / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D054755:Imidazoline Receptors; D007276:Injections, Intraventricular; D008750:Methyldopa / Q000494:pharmacology; D010080:Oxazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011817:Rabbits; D011955:Receptors, Drug / Q000502:physiology*; D000077769:Rilmenidine
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D054755:Imidazoline Receptors; D010080:Oxazoles; D011955:Receptors, Drug; D008750:Methyldopa; D000077769:Rilmenidine