Sympathoinhibitory effects of rilmenidine may be mediated by sites located below the brainstem.
1. To determine the site of action of rilmenidine, we examined its effets on arterial blood pressure (BP), heart rate (HR) and postganglionic renal sympathetic nerve activity (RSNA) after intracerebroventricular (i.c.v.) administration (300 micrograms kg-1), in groups (all n = 6) of conscious and freely moving, pentobarbitone-anaesthetized and pentobarbitone-anaesthetized and spinally transected, fifteen week-old male spontaneously hypertensive rats (SHRs). 2. In conscious SHRs, which exhibited a low sympathetic nerve activity (RSNA: 3.4 +/- 0.9 muV), rilmenidine was inactive on systolic BP (SBP), diastolic BP (DBP), HR and RSNA. 3. In intact pentobarbitone-anaesthetized SHRs, which exhibited an elevated sympathetic nerve activity (RSNA: 10.6 +/- 0.9 muV), rilmenidine exerted potent antihypertensive (delta SBP: -37 +/- 4%; delta DBP: -43 +/- 6%), bradycardic (delta HR: -32 +/- 3%) and sympathoinhibitory (delta RSNA: -68 +/- 9%) activities. 4. In pentobarbitone-anaesthetized SHRs with cervical spinal cord transection, BP was markedly decreased and sympathetic nerve activity (RSNA: 10.3 +/- 3.1 muV) returned to the level observed in conscious SHRs (RSNA: 3.6 +/- 0.5 muV). In these conditions, rilmenidine remained sympathoinhibitory (delta RSNA: -74 +/- 5%). 5. In conclusion, we have shown that pentobarbitone-anaesthesia enhances the peripheral sympathetic tone by a central action, as the spinal cord transection allows RSNA to return to normal levels and that, spinal or ganglionic structures could be a major site of the sympathoinhibitory action of rilmenidine.
Department of Physiology and Clinical Pharmacology, URA-CNRS 606, Faculty of Pharmacy, Lyon, France.
F
F
Sannajust
C
C
Barrès
E
E
Koenig-Bérard
J
J
Sassard
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001933:Brain Stem / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D010424:Pentobarbital; D051381:Rats; D011918:Rats, Inbred SHR; D000077769:Rilmenidine; D013116:Spinal Cord / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects; D013565:Sympatholytics / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D010080:Oxazoles; D013565:Sympatholytics; D010424:Pentobarbital; D000077769:Rilmenidine