TY - JOUR
T1 - The α2-adrenoceptors mediating inhibition of the vasopressor sympathetic outflow in pithed rats
T2 - Pharmacological correlation with α2A, α2B and α2C subtypes
AU - Villamil-Hernández, Ma Trinidad
AU - Alcántara-Vázquez, Oscar
AU - Sánchez-López, Araceli
AU - Centurión, David
N1 - Funding Information:
The technical assistance of José Rodolfo Fernández Calderón and Héctor Vázquez Espinoza is gratefully acknowledged. The authors also thank CONACyT (Mexico) for their financial support (grant number 152534 ).
PY - 2013
Y1 - 2013
N2 - 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 (25 mg/kg) and desipramine (50 μg/kg) and prepared to stimulate the vasopressor sympathetic outflow (T7-T 9) 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 (30 μg/kg min) 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 (0.03-3 Hz). The sympatho-inhibition elicited by B-HT 933 was: (i) unaffected by vehicles (1 ml/kg); (ii) partially antagonised by BRL44408 (300 μg/kg; α2A), imiloxan (3000 μg/kg; α2B) and/or JP-1302 (300 μg/kg; α2C) given separately; and (iii) completely blocked by rauwolscine (300 μg/kg) or the combination of BRL44408 (300 μg/kg)+imiloxan (3000 μg/kg)+JP-1302 (300 μg/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.
AB - 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 (25 mg/kg) and desipramine (50 μg/kg) and prepared to stimulate the vasopressor sympathetic outflow (T7-T 9) 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 (30 μg/kg min) 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 (0.03-3 Hz). The sympatho-inhibition elicited by B-HT 933 was: (i) unaffected by vehicles (1 ml/kg); (ii) partially antagonised by BRL44408 (300 μg/kg; α2A), imiloxan (3000 μg/kg; α2B) and/or JP-1302 (300 μg/kg; α2C) given separately; and (iii) completely blocked by rauwolscine (300 μg/kg) or the combination of BRL44408 (300 μg/kg)+imiloxan (3000 μg/kg)+JP-1302 (300 μg/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.
KW - B-HT 933
KW - BRL44408
KW - Imiloxan
KW - JP-1302
KW - Sympatho-inhibition
KW - α-Adrenoceptors
UR - http://www.scopus.com/inward/record.url?scp=84887032477&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2013.08.025
DO - 10.1016/j.ejphar.2013.08.025
M3 - Artículo
C2 - 24028939
AN - SCOPUS:84887032477
SN - 0014-2999
VL - 718
SP - 245
EP - 252
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -