An investigation into the mechanisms of the cardiovascular effects of 5-hydroxytryptamine in conscious normotensive and DOCA-salt hypertensive rats.
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)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051381:Rats; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014326:Tropanes / Q000494:pharmacology
D012702:Serotonin Antagonists; D014326:Tropanes; C042390:alpha-methylserotonin; D012701:Serotonin; D003900:Desoxycorticosterone; C045918:2-methyl-5-HT; C047087:5-carboxamidotryptamine; C042253:bemesetron