Hemodynamic pharmacology of p-chloroamphetamine, a serotonin agonist, in conscious rats.
The hemodynamic effects of p-chloroamphetamine (PCA), an indirect serotonin (5-HT) agonist, were studied in conscious, unrestrained rats. PCA caused an immediate hypotension and bradycardia followed by a dose-dependent increase in mean arterial pressure (MAP), which lasted for 15 to 60 min, associated with variable effects on heart rate. An intermediate dose increased MAP and resistance in hindquarter and mesenteric, but not renal, vascular beds. The pressor effect of PCA was blocked by prazosin and by 6-hydroxydopamine plus adrenal demedullation, but not by 6-hydroxydopamine or adrenal demedullation separately. Ganglionic blockade with chlorisondamine or beta adrenoceptor blockade with propranolol potentiated the pressor response to PCA, whereas several manipulations of central 5-HT systems (fluoxetine, methysergide and 5,7-dihydroxytryptamine) reduced but did not eliminate the hypertension observed after PCA. The initial bradycardia and hypotension were abolished by chlorisondamine or atropine but not reduced by any other pretreatment, whereas the variable heart rate response was converted to a marked, sustained tachycardia by ganglionic blockade or atropine and to a consistent bradycardia by propranolol and peripheral sympathectomy. The data suggest that PCA causes an immediate central or reflex vagal activation to decrease heart rate and MAP, followed by a central 5-HT-mediated increase in sympathetic activity that increases MAP. Most of the pressor effect observed between 5 and 30 min after PCA appears to be mediated by a direct effect on release of norepinephrine and epinephrine from sympathetic nerve terminals and the adrenal medulla, respectively. Only a minor part of the hemodynamic response to PCA appears to be attributable to its effect on release of 5-HT in the brain.
Alper
R H
RH
Department of Pharmacology, University of Iowa, Iowa City.
Lee
C
C
Brody
M J
MJ
D000313:Adrenal Medulla / Q000502:physiology; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002714:Chlorisondamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D010133:p-Chloroamphetamine / Q000494:pharmacology*
D000662:Amphetamines; D011985:Receptors, Serotonin; D012701:Serotonin; D010133:p-Chloroamphetamine; D001285:Atropine; D002714:Chlorisondamine