title: Streptozotocin-induced diabetes differentially affects sympathetic innervation and control of plantar metatarsal and mesenteric arteries in the rat.
abstract: In humans neural control of arterial vessels supplying skin in the extremities is particularly vulnerable to the effects of diabetes. Here the streptozotocin (STZ) rat model of type 1 diabetes was used to compare effects on neurovascular function in plantar metatarsal arteries (PMAs), which supply blood to skin of hind paw digits, with those in mesenteric arteries (MAs). Twelve weeks after STZ (60 mg/kg ip), wire myography was used to assess vascular function. In PMAs, lumen dimensions were unchanged but both nerve-evoked contractions and sensitivity to α(1) (phenylephrine, methoxamine)- and α(2) (clonidine)-adrenoceptor agonists were reduced. The density of perivascular nerve fibers was also reduced by ~25%. These changes were not observed in PMAs from STZ-treated rats receiving either a low dose of insulin that did not greatly reduce blood glucose levels or a high dose of insulin that markedly reduced blood glucose levels. In MAs from STZ-treated rats, nerve-evoked increases in force did not differ from control but, because lumen dimensions were ~20% larger, nerve-evoked increases in effective transmural pressure were smaller. Increases in effective transmural pressure produced by phenylephrine or α,β-methylene ATP in MAs from STZ-treated rats were not smaller than control, but the density of perivascular nerve fibers was reduced by ~10%. In MAs, the increase in vascular dimensions is primarily responsible for reducing effectiveness of nerve-evoked constrictions. By contrast, in PMAs decreases in both the density of perivascular nerve fibers and the reactivity of the vascular muscle appear to explain impairment of neurovascular transmission.
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Australia.
authors.forename: Niloufer J
authors.initials: NJ
authors.lastname: Johansen
authors.forename: Diana
authors.initials: D
authors.lastname: Tripovic
authors.forename: James A
authors.initials: JA
authors.lastname: Brock
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006614:Hindlimb; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation*; D008682:Metatarsal Bones; D009213:Myography; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000098:blood supply*; D013311:Streptozocin; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013311:Streptozocin; D000255:Adenosine Triphosphate; D009638:Norepinephrine