alpha- and beta-adrenoreceptor-mediated control of brain noradrenaline neurons and antihypertensive therapy.
1. The central noradrenergic nucleus locus coeruleus seems to participate in arousal reactions and cardiovascular modulation. Using single cell recording techniques and biochemical assays, we have studied locus coeruleus neuronal regulation and its interaction with antihypertensive treatments. 2. Acute (5 microgram/kg intravenously) or chronic clonidine treatment (2 microgram/ml in drinking water for 2 weeks) significantly reduced locus coeruleus neuronal activity, probably via activation of alpha 2-receptors within the nucleus. Termination of the chronic regimen increased the noradrenaline cell firing rates above baseline, a finding possibly related to the withdrawal syndrome. 3. In spontaneously hypertensive rats the activation of locus coeruleus neurons by yohimbine, an alpha 2-receptor antagonist, was increased compared with that in normotensive (Wistar-Kyoto) control rats, implying an altered alpha 2-receptor-mediated control of the central noradrenaline neurons. 4. Chronic treatment with DL-propranolol (5 or 10 mg/kg daily for 1 week) but not D-propranolol or acutely given DL-propranolol significantly reduced neuronal activity in the locus coeruleus, an effect which may relate to mental and cardiovascular actions of beta-receptor-blocking drugs. 5. In contrast, chronically given salbutamol, a beta 2-receptor agonist (5 mg/kg subcutaneously for 2 weeks), increased brain noradrenaline utilization. Thus beta-receptors probably participate in the control of brain noradrenaline neurons.
D000200:Action Potentials / Q000187:drug effects; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008125:Locus Coeruleus / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D011941:Receptors, Adrenergic; D015016:Yohimbine; D011433:Propranolol; D003000:Clonidine; D000420:Albuterol; D004298:Dopamine; D009638:Norepinephrine