An investigation into the mechanisms of the cardiovascular effects of 5-hydroxytryptamine in conscious normotensive and DOCA-salt hypertensive rats.

Abstract

The actions of intravenously administered 5-hydroxytryptamine (5-HT) have been analysed in conscious DOCA-salt hypertensive rats using selective 5-HT receptor agonists and antagonists to determine the receptor mechanisms involved and to compare them with those in conscious normotensive rats. In both normotensive and hypertensive rats 5-HT, 3 and 10 micrograms i.v., produced a complex triphasic effect on blood pressure consisting of an initial short lasting depressor response, which was followed by a pressor response and then, finally, a hypotensive phase. Marked decreases in heart rate were observed immediately after dosing, which were followed by small increases in rate. The selective 5-HT3-receptor agonist, 2-methyl 5-HT, 3-30 micrograms i.v., produced immediate and marked dose-related decreases in blood pressure and heart rate in both normotensive and DOCA-salt hypertensive rats. The 5-HT3-receptor antagonist, MDL 72222, 0.03 and 0.1 mg/kg i.v., antagonised these effects in both normotensive and DOCA-salt hypertensive rats. Treatment with MDL 72222, 0.3 mg/kg i.v., abolished the initial depressor response and bradycardia produced by 5-HT. The 5-HT2 receptor agonist, alpha-methyl 5-HT, 3-30 micrograms i.v., produced dose-related increases in blood pressure which were significantly greater in magnitude in DOCA-salt hypertensive than normotensive rats. Bradycardia was observed consistently at 30 micrograms only. The 5-HT 2 receptor antagonist, ketanserin, 0.03-0.3 mg/kg i.v., caused a dose-dependent antagonism of the pressor responses produced by alpha-methyl 5-HT, but had no effect on the increases in blood pressure produced by angiotensin.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: D W Dalton, W Feniuk, P P Humphrey
• Journal: Journal of autonomic pharmacology (J Auton Pharmacol) Vol. 6 Issue 3 Pg. 219-28 (Sep 1986) ISSN: 0144-1795 [Print] England
• PMID: 3771594 (Publication Type: Journal Article)

Chemical References

• Serotonin Antagonists
• Tropanes
• alpha-methylserotonin
• Serotonin
• Desoxycorticosterone
• 2-methyl-5-HT
• 5-carboxamidotryptamine
• bemesetron

Topics

• Animals
• Blood Pressure (drug effects)
• Desoxycorticosterone
• Heart Rate (drug effects)
• Hemodynamics (drug effects)
• Hypertension (chemically induced, physiopathology)
• Male
• Rats
• Serotonin (analogs & derivatives, pharmacology)
• Serotonin Antagonists (pharmacology)
• Tropanes (pharmacology)