Enhanced vascular alpha-adrenergic neuroeffector system in diabetes: importance of calcium

Abstract

Mesenteric arteries from streptozotocin (STZ)-diabetic rats developed greater contractile force in response to norepinephrine and related alpha-agonists than arteries from age-matched controls. Subsequent experiments attempted to define the mechanisms underlying these findings. Transmural nerve stimulation of mesenteric arteries from both groups of animals revealed a similar optimal frequency and voltage of stimulation; however, arteries from STZ-diabetic rats developed greater contractile force than controls. Second, determination of selective alpha-adrenergic antagonist affinities (pA2 values) revealed qualitatively similar postjunctional alpha 1-adrenoceptors in both groups of arteries. Third, disruption of the endothelium did not abolish the enhanced responsiveness of arteries from STZ-diabetic rats. In contrast, the increased vascular responsiveness in STZ-diabetes was associated with a greater dependency on extracellular calcium, with no change in the response to alpha-agonist-induced release of calcium from cellular stores. Thus the enhanced responsiveness of mesenteric arteries from STZ-diabetic rats to alpha-adrenergic agonists cannot be attributed to neuronal deterioration, altered postjunctional alpha-adrenoceptor subtypes, endothelium degeneration, or enhanced release of intracellular calcium but is associated with a greater dependency on extracellular calcium.