Specific Role of α2A‐ and α2B‐, but not α2C‐, Adrenoceptor Subtypes in the Inhibition of the Vasopressor Sympathetic Out‐flow in Diabetic Pithed Rats

• Published in: Basic & clinical pharmacology & toxicology Vol. 117; no. 1; pp. 31 - 38
• Main Authors: Altamirano‐Espinoza, Alain H., Manrique‐Maldonado, Guadalupe, Marichal‐Cancino, Bruno A., Villalón, Carlos M.
• Format: Journal Article
• Language: English
• Published: England 01-07-2015
• Subjects: Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Animals; Blood Pressure - drug effects; Blood Vessels - drug effects; Blood Vessels - innervation; Decerebrate State; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - physiopathology; Electric Stimulation; Male; Rats, Wistar; Receptors, Adrenergic, alpha-2 - drug effects; Receptors, Adrenergic, alpha-2 - metabolism; Sympathetic Nervous System - metabolism; Sympathetic Nervous System - physiopathology; Vasoconstriction - drug effects
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.12354

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.