Differential cardiac sympatho-inhibitory responses produced by the agonists B-HT 933, quinpirole and immepip in normoglycaemic and diabetic pithed rats.

Abstract

This study compared the cardiac sympatho-inhibitory responses produced by agonists at α2 -adrenergic (B-HT933), dopamine D2 -like (quinpirole) and histamine H3 /H4 (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-HT933 (until 100μg/kg per minute) and quinpirole (until 10μg/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 100μg/kg per minute B-HT933 and 10μg/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 10μg/kg per minute), but not in diabetic (until 100μg/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 α2 -adrenergic and dopamine D2 -like receptors, respectively; (ii) the histamine H3 /H4 receptors do not seem to play a sympatho-inhibitory role; and (iii) there is a differential participation of α2 -adrenergic and dopamine D2 -like receptors, which may certainly represent therapeutic targets for the treatment of diabetic complications such as cardiovascular autonomic neuropathy.