Enhanced neuropeptide Y immunoreactivity and vasoconstriction in mesenteric small arteries from the early non-obese...

The present study investigated whether sympathetic neurotransmission is altered at an early stage of diabetes in mesenteric small arteries isolated from female non-obese diabetic (NOD) and control animals without diabetes from the same mouse strain. The NOD diabetic mice had increased plasma glucose and hypertension. Confocal microscopy showed distribution of nerve terminals was similar, but immunoreaction intensity for neuropeptide Y (NPY) and tyrosine hydroxylase was higher in small arteries from NOD diabetic compared with NOD control mice. In the presence of prazosin and activated with vasopressin, electrical field stimulation evoked contractions which were more pronounced in mesenteric arteries from NOD diabetic versus NOD control mice and inhibited by the NPY Y(1) receptor antagonist, BIBP 3226. NPY concentration-response curves were leftward shifted in arteries from NOD diabetic versus NOD control both in arteries with and without endothelium, but not in the presence of the BIBP 3226. The present findings suggest that enhanced NPY content and vasoconstriction to NPY by activation of NPY Y(1) receptors in arteries from diabetic mice may contribute to the enhanced sympathetic nerve activity and vascular resistance in female non-obese early diabetic animals.