Vascular responses to serotonin in steroid hypertensive rats.

Abstract

This study investigates the mechanism responsible for increased vascular sensitivity to serotonin in deoxycorticosterone acetate (DOCA)-salt hypertension. Femoral arteries from normotensive and hypertensive rats were excised and cut into helical strips for isometric force recording. Dose-response curves to serotonin were shifted significantly to the left in arteries from DOCA-salt hypertensive rats compared to those from normotensive rats (ED50:DOCA = 7.1 X 10(-8) M; control = 27 X 10(-8) M). The partial agonistic properties of methysergide were increased in femoral arteries from DOCA-salt hypertensive rats. The competitive antagonism of serotonin by methysergide or ketanserin was similar in arteries from control and DOCA-salt hypertensive rats (pA2: methysergide, control = 10.4, DOCA = 10.5; and ketanserin, control = 10.4, DOCA = 10.4). After cellular calcium (Ca) depletion with EGTA, dose-response curves to Ca were obtained in the presence of serotonin (5.7 X 10(-5) M). The Ca sensitivity of vessels from hypertensive rats was not statistically different from that in arteries from normotensive rats. Contractile responses to serotonin in calcium-free solution following loading of a cellular store with Ca were 50% greater in arteries from DOCA hypertensive rats. These results suggest that the enhanced sensitivity to serotonin in DOCA-salt hypertensive rats is not related to a change in receptor affinity nor to an alteration in transmembrane movement of Ca following receptor activation. The increased serotonin sensitivity is related to an altered mobilization of Ca from a cellular store.