Influence of anaesthesia on the cardiovascular effects of rilmenidine and clonidine in spontaneously hypertensive rats.
1. The acute cardiovascular effects of two alpha 2-adrenoceptor agonists, rilmenidine and clonidine, were studied in 15-week-old male spontaneously hypertensive rats (SHRs). The effects of these drugs were compared with intravenous (i.v.) and intracerebroventricular (i.c.v.) administration in conscious and pentobarbitone-anaesthetized SHRs, in which aortic blood pressure (BP) was continuously recorded. 2. In conscious SHRs, i.v. doses of either rilmenidine (30, 100, 300 micrograms kg-1) or clonidine (3, 10, 30 micrograms kg-1) induced dose-dependent short-lasting increases in BP followed by moderate decreases associated with bradycardia, while the same three doses of both drugs given i.c.v. were devoid of BP and heart rate (HR) effects. 3. Pentobarbitone-anaesthesia increased the sympathetic control of BP and suppressed the cardiac baroreflex sensitivity. 4. In anaesthetized SHRs, i.v. injections of the same 3 doses of rilmenidine and clonidine induced a slight increase in BP, rapidly followed by profound and long-lasting BP and HR decreases. Surprisingly, when given i.c.v., these 3 doses lowered BP and HR to the same extent but in a more progressive manner. 5. The lack of efficacy of both drugs in conscious SHRs after the i.c.v. administration of i.v. active doses and the lack of more marked and rapid effects in anaesthetized SHRs, after i.c.v. than after i.v. injections, question the involvement of a major central site of action for these antihypertensive alpha 2-adrenoceptor agonists. Moreover, these results show that the cardiovascular effects of these drugs are profoundly influenced by baseline sympathetic nervous system activity which is enhanced by pentobarbitone-anaesthesia.
Department of Physiology and Clinical Pharmacology, URA-CNRS 606, Faculty of Pharmacy, Lyon, France.
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Sannajust
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Cerutti
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Koenig-Bérard
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Sassard
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D010080:Oxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D010424:Pentobarbital; D051381:Rats; D011918:Rats, Inbred SHR; D012018:Reflex / Q000187:drug effects; D000077769:Rilmenidine; D013564:Sympathetic Nervous System / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D010080:Oxazoles; D010424:Pentobarbital; D003000:Clonidine; D000077769:Rilmenidine