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.

Abstract

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.

• Authors: K Chaouche-Teyara, B Fournier, M Safar, H Dabiré
• Journal: Clinical and experimental hypertension (New York, N.Y. : 1993) (Clin Exp Hypertens) Vol. 16 Issue 6 Pg. 779-98 (Nov 1994) ISSN: 1064-1963 [Print] England
• PMID: 7858559 (Publication Type: Journal Article)

Chemical References

• Amphetamines
• Ergolines
• Serotonin Antagonists
• Serotonin Receptor Agonists
• alpha-methylserotonin
• Serotonin
• Spiperone
• LY 53857
• 4-iodo-2,5-dimethoxyphenylisopropylamine

Topics

• Amphetamines (administration & dosage, pharmacology)
• Animals
• Dose-Response Relationship, Drug
• Ergolines (pharmacology)
• Hemodynamics (drug effects)
• Injections, Intravenous
• Injections, Intraventricular
• Male
• Rats
• Rats, Wistar
• Regional Blood Flow (drug effects)
• Renal Circulation (drug effects)
• Serotonin (administration & dosage, analogs & derivatives, pharmacology)
• Serotonin Antagonists (pharmacology)
• Serotonin Receptor Agonists (administration & dosage, pharmacology)
• Spiperone (pharmacology)
• Splanchnic Circulation (drug effects)