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Differential cardiac sympatho‐inhibitory responses produced by the agonists B‐ HT 933, quinpirole and immepip in normoglycaemic and diabetic pithed rats
Author(s) -
RiveraMancilla Eduardo,
AltamiranoEspinoza Alain H,
ManriqueMaldonado Guadalupe,
VillanuevaCastillo Belinda,
Villalón Carlos M
Publication year - 2018
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12949
Subject(s) - quinpirole , endocrinology , medicine , stimulation , receptor , dopamine , chemistry , adrenergic , agonist
Summary This study compared the cardiac sympatho‐inhibitory responses produced by agonists at α 2 ‐adrenergic (B‐ HT 933), dopamine D 2 ‐like (quinpirole) and histamine H 3 /H 4 (immepip) receptors between normoglycaemic and streptozotocin‐pretreated (diabetic) pithed rats. Intravenous (i.v.) continuous infusions of B‐ HT 933, quinpirole or immepip were used in normoglycaemic and diabetic pithed rats to analyse their sympatho‐inhibitory effects on the electrically‐stimulated cardioaccelerator sympathetic outflow. Both in normoglycaemic and diabetic animals, B‐ HT 933 (until 100 μg/kg per minute) and quinpirole (until 10 μg/kg per minute) inhibited the tachycardic responses to electrical sympathetic stimulation, but not those to i.v. bolus of exogenous noradrenaline. These sympatho‐inhibitory responses were more pronounced in diabetic than in normoglycaemic animals. Accordingly, the areas under the curve for 100 μg/kg per minute B‐ HT 933 and 10 μg/kg per minute quinpirole in diabetic rats (1065 ± 70 and 920 ± 35, respectively) were significantly smaller ( P < .05) than those in normoglycaemic rats (1220 ± 45 and 1360 ± 42, respectively). In contrast, immepip infusions produced cardiac sympatho‐inhibition in normoglycaemic (until 10 μg/kg per minute), but not in diabetic (until 100 μg/kg per minute) animals. Our results suggest that in diabetic pithed rats: (i) the more pronounced cardiac sympatho‐inhibition to B‐ HT 933 and quinpirole may be probably due to up‐regulation of α 2 ‐adrenergic and dopamine D 2 ‐like receptors, respectively; (ii) the histamine H 3 /H 4 receptors do not seem to play a sympatho‐inhibitory role; and (iii) there is a differential participation of α 2 ‐adrenergic and dopamine D 2 ‐like receptors, which may certainly represent therapeutic targets for the treatment of diabetic complications such as cardiovascular autonomic neuropathy.