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Specific Role of α 2A ‐ and α 2B ‐, but not α 2C ‐, Adrenoceptor Subtypes in the Inhibition of the Vasopressor Sympathetic Out‐flow in Diabetic Pithed Rats
Author(s) -
AltamiranoEspinoza Alain H.,
ManriqueMaldonado Guadalupe,
MarichalCancino Bruno A.,
Villalón Carlos M.
Publication year - 2015
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12354
Subject(s) - rauwolscine , medicine , endocrinology , antagonist , stimulation , ed50 , agonist , bolus (digestion) , diabetes mellitus , chemistry , yohimbine , receptor
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 α 2 ‐adrenoceptor agonists within central and peripheral α 2 ‐adrenoceptors (e.g. profound antinociceptive effects in diabetic subjects). Hence, this study investigated the pharmacological profile of the α 2 ‐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 α 2 ‐adrenoceptor agonist and rauwolscine as a non‐selective α 2A/2B/2C ‐adrenoceptor antagonist; in addition, BRL 44408, imiloxan and JP ‐1302 were used as subtype‐selective α 2A ‐, α 2B ‐ and α 2C ‐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 ED 50 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 α 2C ‐adrenoceptors.