title: Specific role of α2A - and α2B -, but not α2C -, adrenoceptor subtypes in the inhibition of the vasopressor sympathetic out-flow in diabetic pithed rats.
abstract: Several lines of evidence have shown an association of diabetes with a catecholamines' aberrant homeostasis involving a drastic change in the expression of adrenoceptors. This homeostatic alteration includes, among other things, atypical actions of α2 -adrenoceptor agonists within central and peripheral α2 -adrenoceptors (e.g. profound antinociceptive effects in diabetic subjects). Hence, this study investigated the pharmacological profile of the α2 -adrenoceptor subtypes that inhibit the vasopressor sympathetic out-flow in streptozotocin-pre-treated (diabetic) pithed rats. For this purpose, B-HT 933 (up to 30 μg/kg min) was used as a selective α2 -adrenoceptor agonist and rauwolscine as a non-selective α2A/2B/2C -adrenoceptor antagonist; in addition, BRL 44408, imiloxan and JP-1302 were used as subtype-selective α2A -, α2B - and α2C -adrenoceptor antagonists, respectively (all given i.v.). I.v. continuous infusions of B-HT 933 inhibited the vasopressor responses induced by electrical sympathetic stimulation without affecting those by i.v. bolus injections of noradrenaline in both normoglycaemic and diabetic rats. Interestingly, the ED50 for B-HT 933 in diabetic rats (25 μg/kg min) was almost 1-log unit greater than that in normoglycaemic rats (3 μg/kg.min). Moreover, the sympatho-inhibition induced by 10 μg/kg min B-HT 933 in diabetic rats was (i) abolished by 300 μg/kg rauwolscine or 100 and 300 μg/kg BRL 44408; (ii) partially blocked by 1000 μg/kg imiloxan; and (iii) unchanged by 1000 μg/kg JP-1302. Our findings, taken together, suggest that B-HT 933 has a less potent inhibitory effect on the sympathetic vasopressor responses in diabetic (compared to normoglycaemic) rats and that can probably be ascribed to a down-regulation of α2C -adrenoceptors.
authors.affiliation: Deparment of pharmaco-biology, Cinvestav-Coapa, Tlalpan, Mexico D.F., Mexico.
authors.forename: Alain H
authors.initials: AH
authors.lastname: Altamirano-Espinoza
authors.affiliation: Deparment of pharmaco-biology, Cinvestav-Coapa, Tlalpan, Mexico D.F., Mexico.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Manrique-Maldonado
authors.affiliation: Deparment of pharmaco-biology, Cinvestav-Coapa, Tlalpan, Mexico D.F., Mexico.
authors.forename: Bruno A
authors.initials: BA
authors.lastname: Marichal-Cancino
authors.affiliation: Deparment of pharmaco-biology, Cinvestav-Coapa, Tlalpan, Mexico D.F., Mexico.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Villalón
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000294:innervation*; D003655:Decerebrate State; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D004558:Electric Stimulation; D008297:Male; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism* / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: C547770:Adra2a protein, rat; C547773:Adra2b protein, rat; C547776:Adra2c protein, rat; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018341:Receptors, Adrenergic, alpha-2