Hypotensive and hypertensive effects of catecholamines intrathecally injected in anesthetized rats.
The cardiovascular effects of catecholamines intrathecally (i.t.) injected at the T12-L1 level were analyzed in pentobarbital anesthetized rats. Volumes of injection were not greater than 3 microliters. Noradrenaline in doses ranging from 0.03 to 0.3 micrograms (i.t.) did not alter the mean blood pressure (MBP) while higher doses (1, 3 and 10 micrograms, i.t.) caused a dose-dependent increase in MBP. Adrenaline induced hypotensive effects at low doses (0.03-0.3 micrograms i.t.) and pressor effects at high doses (3 and 10 micrograms, i.t.). Neither adrenaline nor noradrenaline modified the heart rate. The pressor responses to both catecholamines were antagonized by the alpha 1-adrenoceptor blocker prazosin (0.05-1 microgram, i.t.) and by the selective alpha 1A-adrenoceptor antagonist 5-methyl urapidil (10 and 15 micrograms, i.t.). In contrast, these pressor effects were not modified by the alpha 1B-adrenoceptor antagonist chloroethylclonidine (90 micrograms i.t.). In animals pretreated with 1 microgram prazosin (i.t.), low doses of noradrenaline (0.03 and 0.1 microgram, i.t.) caused a hypotensive effect. Prazosin (1 microgram i.t.) failed to alter the hypotension caused by 0.1 microgram adrenaline. The hypotensive response induced by either 0.1 microgram noradrenaline (in the presence of prazosin) or 0.1 microgram adrenaline was blocked by the alpha 2-adrenoceptor antagonist yohimbine (1 mg/kg, i.v.), by the GABA-A antagonists bicuculline (3.2 micrograms, i.t.) and picrotoxin (2.7 micrograms, i.t.), and by the GABA-B antagonist 2-hydroxy saclofen (30 micrograms, i.t.). The glycine-receptor antagonist strychnine (25 micrograms, i.t.) did not modify the hypotension induced by either noradrenaline (in the presence of prazosin) or adrenaline. These findings suggest that in the low thoracolumbar spinal cord of pentobarbital-anesthetized rats, noradrenaline and adrenaline have excitatory as well as inhibitory effects on the control of the BP. The pressor responses of high doses of i.t. injected catecholamines could be mediated by the activation of spinal alpha 1A-adrenoceptors, although the participation of alpha 1B-adrenoceptors cannot be rule out entirely. The hypotensive responses induced by low doses of i.t. injected catecholamines seem to involve the activation of spinal alpha 2A-adrenoceptors and the stimulation of an inhibitory GABAergic neuron in the spinal cord.
del Carmen García
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Cátedra de Farmacología, Facultad de Farmacia y Bioquímica (UBA), Buenos Aires, Argentina.
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Celuch
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D000322:Adrenergic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D004837:Epinephrine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D018684:Glycine Agents / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D002395:Catecholamines; D018684:Glycine Agents; D005680:gamma-Aminobutyric Acid; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine