Enhanced vascular alpha-adrenergic neuroeffector system in diabetes: importance of calcium.
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.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006143:Guanabenz / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation / Q000503:physiopathology; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000294:innervation* / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015016:Yohimbine; D006143:Guanabenz; D008729:Methoxamine; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin