Renal denervation altered the hemodynamic and renal effects following intracerebroventricular administration of the I1-imidazoline receptor agonist, rilmenidine, in pentobarbital anaesthetized rats.
Previous studies have reported on the effects of intracerebroventricular (icv) administration of the I1-imidazoline receptor agonist moxonidine. In the present study, the relationship between increasing doses of the I1-agonist rilmenidine (administered icv) with blood pressure and renal function has been determined. Moreover, the importance of the renal nerves in this response have also been assessed. In pentobarbitone anesthetized rats, icv rilmenidine (30, 100, 300 nmol in 5 microliters) produced a dose related decrease in blood pressure and heart rate. Urine flow was not altered at the lower doses although at the highest dose (300 nmol) the increase approached significance (p = 0.06). Sodium excretion and osmolar clearance were not altered. Free water clearance was increased at 100 and 300 nmol rilmenidine (p < 0.05). Consistent with the above dose response studies, in sham denervated rats icv rilmenidine (300 nmol) decreased blood pressure and increased free water clearance. In rats having undergone renal denervation, baseline levels of urine flow rate, sodium excretion and osmolar clearance were increased. In these denervated rats, icv rilmenidine (300 nmol) failed to decrease blood pressure. Urine flow rate was increased with a decrease in sodium excretion and osmolar clearance. Free water clearance was increased. These results indicate the importance of the renal nerves in mediating the acute decrease in blood pressure following icv administration of the I1-imidazoline receptor agonist rilmenidine. The increase in free water clearance seen following icv rilmenidine appears to be mediated independent of the renal nerves. The changes associated with sodium excretion on the contrary are dependent on intact renal nerves.
Penner
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SB
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Smyth
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DD
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D054755:Imidazoline Receptors; D007276:Injections, Intraventricular; D007668:Kidney / Q000187:drug effects* / Q000294:innervation*; D009318:Natriuresis / Q000187:drug effects; D009994:Osmolar Concentration; D010080:Oxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D010424:Pentobarbital; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000819:agonists*; D000077769:Rilmenidine
D054755:Imidazoline Receptors; D010080:Oxazoles; D011955:Receptors, Drug; D010424:Pentobarbital; D000077769:Rilmenidine