Ritanserin and serotonergic mechanisms in blood pressure and fluid regulation in sheep.
1. In previous studies, exogenous serotonin (5-HT), administered intravenously, caused dose-related increases in mean arterial pressure and heart rate in conscious sheep. The 5-HT2 antagonist ketanserin (0.1 mg/kg per h, i.v.) was shown to lower blood pressure in the conscious sheep primarily through antagonism of alpha-adrenoceptors. 2. A newer 5-HT2 antagonist, ritanserin, is a more selective antagonist in vivo, as it attenuated or abolished pressor responses to exogenous 5-HT, but not to phenylephrine. 3. When infused alone, ritanserin (0.1 mg/kg per h, i.v.) failed to produce a decrease in blood pressure, suggesting that 5-HT antagonistic properties are not sufficient by themselves to lower blood pressure. 4. Ritanserin displayed a different metabolic profile to ketanserin, with a markedly decreased water intake. The mechanism of this effect is unresolved, but may imply a permissive role for 5-HT in the modulation of drinking responses in the sheep. 5. Ritanserin did not modify ACTH-induced hypertension in sheep.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy; D007650:Ketanserin / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D016713:Ritanserin; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D012756:Sheep; D014882:Water-Electrolyte Balance / Q000187:drug effects*
D010880:Piperidines; D012702:Serotonin Antagonists; D016713:Ritanserin; D010656:Phenylephrine; D012701:Serotonin; D007650:Ketanserin