Serotonergic mechanisms and blood pressure in sheep

This study examined the effects of the serotonergic (5-HT2) antagonist ketanserin in sheep on haemodynamic responses to infused serotonin (5-HT), development of adrenocorticotrophin (ACTH)-induced hypertension, and the effect of ACTH on in vivo pressor responsiveness to 5-HT. Serotonin produced a dose-related increase in mean arterial pressure and heart rate. These increases in mean arterial pressure were attenuated or abolished by ketanserin, but increases in heart rate were enhanced. Ketanserin modified the pressure response to the alpha-adrenergic agonist phenylephrine, and did not further lower mean arterial pressure in sheep pretreated with the alpha-antagonist prazosin. Thus, ketanserin exhibits alpha-adrenergic antagonism in sheep. Ketanserin infusion lowered mean arterial pressure in normal sheep but did not affect the pressor response to ACTH infusion. There was no difference in pressor responsiveness to 5-HT (0.1-30 micrograms/kg) before and after ACTH treatment. Thus, 5-HT raises mean arterial pressure in sheep in a dose-related fashion, but there is no evidence of a role for 5-HT in ACTH-induced hypertension.