title: Interaction of the dopamine D2 receptor agonist quinpirole with sympathetic vasomotor tone and the central action of rilmenidine in conscious rabbits.
abstract: Previous studies in conscious rats have shown that systemic administration of the dopamine D2 receptor agonist quinpirole causes a centrally-mediated increase in blood pressure which is associated with increased plasma levels of noradrenaline and adrenaline. In addition, treatment with quinpirole caused a marked inhibition of the antihypertensive effect of centrally-acting sympatho-inhibitory drugs such as clonidine, rilmenidine and alpha-methyldopa, suggesting an interaction at the level of sympathetic vasomotor tone. The main aim of the present study was investigate in conscious rabbits the effect of quinpirole on renal sympathetic nerve activity. In addition, we studied the effect of pretreatment with quinpirole on responses to additional quinpirole injections or rilmenidine treatment. Quinpirole treatment caused a prolonged dose-dependent increase in blood pressure and heart rate. Additional injection of quinpirole, 30 min after the first treatment, caused a significantly smaller pressor response (7+/-2 vs. 17+/-2 mm Hg). Injection of rilmenidine caused a larger decrease in blood pressure in rabbits which had been pretreated with quinpirole than in controls (-28+/-3 vs. -14+/-3 mm Hg). Total renal sympathetic nerve activity was markedly increased by quinpirole treatment (3.5-fold), an effect which could be attributed to both increased amplitude and increased frequency of the renal nerve signal. After a second injection of quinpirole, 30 min after the first treatment, only total renal sympathetic nerve activity and amplitude were increased and the effects were reduced. These results show marked actions of quinpirole on renal sympathetic nerve activity in conscious rabbits. However, the previously described apparent desensitisation to the antihypertensive effect of rilmenidine could not be observed in rabbits, suggesting marked species differences in the mechanism and site of action of rilmenidine.
authors.affiliation: Neuropharmacology Laboratory, Baker Medical Research Institute, Melbourne, Victoria, Australia. maarten.vandenbuuse@baker.edu.au
authors.forename: M
authors.initials: M
authors.lastname: van den Buuse
authors.forename: S B
authors.initials: SB
authors.lastname: Tritton
authors.forename: S L
authors.initials: SL
authors.lastname: Burke
authors.forename: G A
authors.initials: GA
authors.lastname: Head
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation*; D010080:Oxazoles / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology*; D011817:Rabbits; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D000077769:Rilmenidine; D013564:Sympathetic Nervous System / Q000187:drug effects*
chemical_list: D000316:Adrenergic alpha-Agonists; D018491:Dopamine Agonists; D010080:Oxazoles; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D000077769:Rilmenidine