Vascular responses to serotonin in steroid hypertensive rats.
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.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003900:Desoxycorticosterone; D004305:Dose-Response Relationship, Drug; D005263:Femoral Artery / Q000187:drug effects* / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D007650:Ketanserin; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D010880:Piperidines; D011985:Receptors, Serotonin; D012701:Serotonin; D003900:Desoxycorticosterone; D007650:Ketanserin; D002122:Calcium Chloride; D002118:Calcium; D009638:Norepinephrine; D008784:Methysergide