Antihypertensive Effect of 5-HT<sub>1A</sub> Agonist Buspirone and 5-HT<sub>2B</sub> Antagonists in Experimentally Induced Hypertension in Rats

We investigated the antihypertensive effect of 5-HT1A agonist (buspirone) and 5-HT2B antagonists (SB204741 and SB200646) in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats. Experiments were divided into two sets: in the first set, sham-operated control and DOCA-treated hypertensive rats received buspirone (1 mg/kg/day p.o. for 4 weeks) and in the second set, in vivo and in vitro studies were carried out. In the case of in vivo studies, sham-operated control and DOCA-treated hypertensive rats received SB204741 or SB200646 (1 mg/kg/week i.v. for 4 weeks). Blood pressure was measured weekly by tail-cuff method. After completion of the treatment schedule, blood pressure and vascular reactivity to various agonists like 5-HT, noradrenaline and adrenaline were recorded. Chronic administration of buspirone, SB204741 and SB200646 produced a significant reduction in blood pressure and vascular reactivity to agonists in DOCA-salt hypertensive rats, implying an antihypertensive effect. However, chronic administration of the same drugs in sham control rats did not alter blood pressure and vascular reactivity to various agonists. For in vitro studies a similar treatment schedule was followed as in vivo studies and a cumulative concentration response curve of 5-HT was recorded on isolated thoracic aorta. Treatment with 5-HT2B antagonists shifted the concentration response curve of 5-HT to the right on isolated aorta. We conclude that 5-HT1A agonist and 5-HT2B antagonists possess an antihypertensive effect.