Abstract:
SUMMARY:The present study reports the effects of apomorphine (APO) on blood pressure and the principal site of action of this agonist in 4-week deoxycorticosterone-acetate (DOCA)-hypertensive conscious rats. In these preprations, intravenous (i.v.) administration of APO (0.50-1 mg/kg) induced short-lasting and dose-dependent decreases in mean arterial pressure. The hypotensive response to APO (0.3 mg/kg) was reversed into a significant pressor effect by i.v. hexamethonium (30 mg/kg), whereas it was enhanced by i.v. pretreatment with the vasopressor antagonist of arginine vasopressin (AVP) d(CH2)5Tyr(Me)AVP (10 microg/kg) and/or prazosin (1 mg/kg). This depressor effect was suppressed by the central and peripheral dopamine D2 receptor antagonist metoclopramide (5 mg/kg i.v.), unaffected by the selective dopamine D1 receptor antagonist SCH 23390 (0.2 mg/kg i.v.), partly reduced by intrathecal domperidone (40 microg per rat at T9-T10 level), a dopamine D2 receptor antagonist which does not cross the blood-brain barrier, and reversed into a significant pressor effect by i.v. domperidone (0.5 mg/kg). The latter pressor effect was fully abolished by combined i.v. pretreatment with the vasopressor antagonist of AVP and prazosin. These results show that, in conscious DOCA salt-hypertensive rats, APO induced a brief, initial depressor effect, which is opposed to a central pressor component. The depressor component is related to an inhibition of norepinephrine transmission through activation of dopamine D2 receptors, some of which are located in the spinal cord and some of which are located in the peripheral circulation. The central pressor component, which became manifest after peripheral dopamine D2 receptor blockade, appears to be related to an increase in vasopressin release and sympathetic tone through activation of brain dopamine D2 receptors.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Toscano CF,Lahlou Sdoi
10.1097/00005344-200312000-00012subject
Has Abstractpub_date
2003-12-01 00:00:00pages
772-81issue
6eissn
0160-2446issn
1533-4023journal_volume
42pub_type
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journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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pub_type: 临床试验,杂志文章,随机对照试验
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