Effects of serotonin antagonists on blood pressure in mineralocorticoid hypertensive sheep

The serotonin antagonist methysergide has a partial agonistic action on isolated vascular smooth muscle from hypertensive animais, whereas ketanserin, another serotonin antagonist, does not. The goal of this study was to determine the effects of these two agents on blood pressure in the conscious, deoxycorticosterone acetate (DOCA) hypertensive sheep. Adult sheep maintained on a standard laboratory diet and 0.1% NaCl/0.25% KCl drinking water developed hypertension fol-lowing DOCA implantation (mean arterial pressure: control = 83 mm Hg, DOCA = 108 mm Hg). Methysergide (40 μg/kg-i.v. bolus) produced a greater pressor response in hypertensive sheep than in normotensive sheep (control = 8 ± 1 mm Hg, DOCA = 18 ± 3 mm Hg). Ketanserin (50 μg/kg-i.v. bolus), on the other hand, caused a similar decrease in blood pressure (∼-16 mm Hg) in both control and DOCA sheep. Pressor responses to infusions of serotonin were greater in DOCA sheep compared with controls. Both methysergide and ketanserin were equally effective antagonists of a serotonin-induced pressor response (75% inhibition) in control and DOCA sheep. Methysergide had no effect on a norepinephrine-induced pressor response, but ketanserin caused a 20% attenuation of this response. These results demonstrate an enhanced responsiveness to serotonin and methysergide in DOCA hypertensive sheep.