Study on the mechanism of 5-HT-induced tachycardia in the pithed rat.
1. Intravenous infusion of serotonin (5-HT) (2.5, 5, 10 and 20 micrograms/kg/min) in pithed rats induced a dose-dependent sustained tachycardia. 2. Pretreatment by phentolamine or diltiazem did not modify the chronotropic response to 5-HT. In contrast, atenolol antagonized this tachycardia and the 5-HT antagonists methysergide, ketanserin and MDL 72222 reduced it. 3. The 5-HT-induced tachycardia was abolished by desipramine and was not affected by fluvoxamine, a specific 5-HT uptake inhibitor. Surrenalectomy did not change the response to 5-HT but catecholamine depletion by reserpine markedly inhibited it. 4. Infusion of 5-HT increased the ratio of noradrenaline (NA) in the heart to NA in plasma, from 1.70 in control group to 2.76 in treated group (P less than 0.05). Desipramine inhibited this effect. 5. It was concluded that the tachycardia induced by an infusion of 5-HT in pithed rat results from a complex mechanism involving mainly the release of NA from the cardiac sympathetic nerves and a less important direct 5-HT2 mechanism.
Midol-Monnet
M
M
Laboratoire de Pharmacologie, U.A.-C.N.R.S. 594, Faculté de Pharmacie, Chatenay-Malabry, France.
Heimburger
M
M
Davy
M
M
Beslot
F
F
Cohen
Y
Y
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003655:Decerebrate State; D003891:Desipramine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000097:blood / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology
D014326:Tropanes; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C042253:bemesetron; D003891:Desipramine; D009638:Norepinephrine