The α2-adrenoceptors mediating inhibition of the vasopressor sympathetic outflow in pithed rats: Pharmacological correlation with α2A, α2B and α2C subtypes
α2-Adrenoceptors were first described as presynaptic receptors inhibiting the release of various transmitters from neurons in the central and peripheral nervous systems. In vitro studies have confirmed that α2A, α2B and α2C subtypes inhibited noradrenaline release from postganglionic sympathetic neu...
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Published in | European journal of pharmacology Vol. 718; no. 1-3; pp. 245 - 252 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier B.V
15.10.2013
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Subjects | |
Online Access | Get full text |
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Summary: | α2-Adrenoceptors were first described as presynaptic receptors inhibiting the release of various transmitters from neurons in the central and peripheral nervous systems. In vitro studies have confirmed that α2A, α2B and α2C subtypes inhibited noradrenaline release from postganglionic sympathetic neurons but no study has been reported their involvement in the vasopressor sympathetic outflow in vivo. Thus, this study analysed the subtype(s) involved in the inhibition produced by the α2-adrenoceptor agonist, B-HT 933, on the vasopressor sympathetic outflow. Male Wistar pithed rats were pre-treated with i.v. bolus injections of gallamine (25mg/kg) and desipramine (50µg/kg) and prepared to stimulate the vasopressor sympathetic outflow (T7–T9) or to receive i.v. bolus of exogenous noradrenaline. Sympathetic stimulation or exogenous noradrenaline produced, respectively, frequency-dependent and dose-dependent vasopressor responses. I.v. continuous infusion of B-HT 933 (30μg/kgmin) failed to modify the vasopressor responses to exogenous noradrenaline and inhibited those induced by preganglionic stimulation of the vasopressor sympathetic outflow at all frequencies of stimulation (0.03–3Hz). The sympatho-inhibition elicited by B-HT 933 was: (i) unaffected by vehicles (1ml/kg); (ii) partially antagonised by BRL44408 (300μg/kg; α2A), imiloxan (3000μg/kg; α2B) and/or JP-1302 (300μg/kg; α2C) given separately; and (iii) completely blocked by rauwolscine (300μg/kg) or the combination of BRL44408 (300μg/kg)+imiloxan (3000μg/kg)+JP-1302 (300μg/kg). The above doses of antagonists did not modify per se the sympathetically-induced vasopressor responses. These results suggest that the vasopressor sympatho-inhibition to B-HT 933 is primarily mediated by activation of α2A/2B/2C-adrenoceptors in pithed rats. |
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Bibliography: | http://dx.doi.org/10.1016/j.ejphar.2013.08.025 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0014-2999 1879-0712 |
DOI: | 10.1016/j.ejphar.2013.08.025 |