Systemic and regional haemodynamic effects of 1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane (DOI) and alpha-methyl-5-HT, in the anaesthetised rat.
The present experiment was performed to investigate the haemodynamic effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) in the anaesthetised normotensive rat. DOI (1-300 micrograms/kg i.v.) increased mean arterial pressure (MAP), total peripheral resistance (TPR) and decreased cardiac output (CO) and heart rate (HR). DOI increased all vascular resistances investigated (hindquarters, mesenteric and renal). Alpha-methyl-5-HT (10-300 micrograms/kg i.v.) dose-dependently increased MAP, TPR, all regional vascular resistances and decreased CO and HR. The bradycardia induced by alpha-methyl-5-HT was suppressed by bivagotomy. Both DOI and alpha-methyl-5-HT were more effective on renal vascular bed than hindquarters and mesenteric vascular beds. The effects of DOI and alpha-methyl-5-HT were antagonised by spiperone (10 or 100 micrograms/kg i.v.) and LY 53857 (10 micrograms/kg i.v.). Intracerebroventricular administration of DOI (100 micrograms/kg) increased MAP, TPR, regional vascular resistances and did not change HR and CO. Pretreatment with xylamidine (10 micrograms/kg i.v.), a selective peripheral 5-HT2 receptor antagonist, blocked i.v. and i.c.v. effects of DOI. These results suggest that: 1) the increase in MAP induced by DOI and alpha-methyl-5-HT is due to an increase in TPR. All regional vascular beds and in particular the renal vascular bed participate in the increase of TPR. 2) Peripheral--and may be--central 5-HT2 receptors seem to be implicated in the control of regional vascular resistances. 3) Cardiac effects of alpha-methyl-5-HT are baroreflexly-mediated whereas those of DOI are--at least in part--centrally mediated.
INSERM U 337, Faculté de Médecine Broussais Hôtel-Dieu, Paris, France.
K
K
Chaouche-Teyara
B
B
Fournier
M
M
Safar
H
H
Dabiré
D000662:Amphetamines / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000187:drug effects
D000662:Amphetamines; D004873:Ergolines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C042390:alpha-methylserotonin; D012701:Serotonin; D013134:Spiperone; C032663:LY 53857; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine