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Cardiovascular responses to intrathecal dopamine receptor agonists in conscious DOCA‐salt hypertensive rats
Author(s) -
Lahlou Saad
Publication year - 1999
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1999.tb00373.x
Subject(s) - quinpirole , apomorphine , endocrinology , medicine , agonist , dopamine agonist , domperidone , dopamine , bradycardia , dopamine receptor , dopaminergic , anesthesia , heart rate , blood pressure , receptor
— Previous studies have demonstrated that in conscious deoxycorticosterone acetate (DOCA)‐salt hypertensive rats, the hypotensive action of intravenous (i.v.) bromocriptine, a selective dopamine D 2 receptor agonist, was mediated partly by peripheral and partly by spinal dopamine D 2 receptor stimulation, and that this effect was greater and longer‐lasting than that in uninephrectomized control rats. To determine whether this amplification results partly from a putative spinal hypersensitivity phenomenon, cardiovascular responses to intrathecal (i.t.) administration of apomorphine and quinpirole were studied in conscious, 4‐week DOCA‐salt hypertensive rats and compared with those in uninephrectomized control rats. In both groups, upper thoracic (T 2 ‐T 4 ) i.t. injections of apomorphine (9.1, 45.5 and 91.1 μg/rat) induced immediate and dose‐dependent decreases in mean aortic pressure (MAP) and heart rate (HR), while i.t. quinpirole (38.4 μg/rat) induced only bradycardia. Neither magnitude nor duration of these responses was enhanced in DOCA‐salt hypertensive rats when compared to control rats. In DOCA‐salt hypertensive rats, apomorphine‐induced hypotension and bradycardia remained unaffected by i.v. (500 μg/kg) pretreatment with domperidone, a selective dopamine D 2 receptor antagonist that does not cross the blood‐brain barrier. However, i.t. (40 μg/rat at T 2 ‐T 4 ) pretreatment with domperidone significantly reduced apomorphine‐induced hypotension, but fully suppressed bradycardia elicited by either apomorphine or quinpirole. These results demonstrated that in conscious DOCA‐salt hypertensive rats, intrathecally‐injected apomorphine or quinpirole decreased MAP and or HR through a spinal D 2 dopaminergic mechanism, as previously demonstrated in normotensive intact rats. Since both magnitude and duration of these responses were unchanged with respect to uninephrectomized control rats, enhancement of the hypotensive effect of intravenously‐administered bromocriptine in DOCA‐salt hypertensive rats does not appear to involve spinal dopamine D 2 receptors.