Cardiovascular responses to central clonidine, alpha-methyldopa, and 6-hydroxydopamine in conscious normotensive and spontaneously hypertensive rats following naloxone.
The possible involvement of endogenous opioid peptides in the cardiovascular responses observed following central alpha-adrenoceptor stimulation with clonidine, alpha-methyldopa (alpha-MD), and 6-hydroxydopamine (6-OHDA) was examined in conscious normotensive Wistar and spontaneously hypertensive (SHR) rats. Clonidine [2.5 micrograms intracisternally (i.c.)] produced rapid hypotension (-36 +/- 2 mm Hg) and bradycardia (-53 +/- 5 beats/min) in SHR that were similar to observations in animals given either naloxone (50 micrograms i.c. or 10 mg/kg i.p.) or appropriate saline control injections. Peripheral doses of naloxone (1-2 mg/kg) or saline did not further change arterial pressure or heart rate in either Wistar rats or SHR given alpha-MD (1.0 mg i.c.) 3 h earlier. In addition, central doses of naloxone (3 X 50 micrograms i.c.) given at hourly intervals did not affect the responses to alpha-MD. Central administration of 6-OHDA acutely releases noradrenaline which produces an initial fall in arterial blood pressure and heart rate. Intracisternal 6-OHDA (400 micrograms) produced similar time course and maximum circulatory effects in rats given naloxone (50 micrograms i.c. before and at each subsequent hour) as in saline-treated animals. Naloxone (1 mg/kg s.c.) significantly attenuated morphine-induced analgesia. These findings do not support a critical role of endogenous opioids in mediating the acute antihypertensive actions of clonidine and alpha-MD or in the cardiovascular responses produced by noradrenaline release following central 6-OHDA.
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006892:Hydroxydopamines / Q000494:pharmacology*; D008297:Male; D008750:Methyldopa / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D016627:Oxidopamine; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects
D006892:Hydroxydopamines; D011942:Receptors, Adrenergic, alpha; D009270:Naloxone; D008750:Methyldopa; D016627:Oxidopamine; D003000:Clonidine