Alterations in perivascular innervation function in mesenteric arteries from offspring of diabetic rats

Br J Pharmacol. 2015 Oct;172(19):4699-713. doi: 10.1111/bph.13244. Epub 2015 Aug 14.

Abstract

Background and purpose: We have reported that exposure to a diabetic intrauterine environment during pregnancy increases blood pressure in adult offspring, but the mechanisms involved are not completely understood. This study was designed to analyse a possible role of perivascular sympathetic and nitrergic innervation in the superior mesenteric artery (SMA) in this effect.

Experimental approach: Diabetes was induced in pregnant Wistar rats by a single injection of streptozotocin. Endothelium-denuded vascular rings from the offspring of control (O-CR) and diabetic rats (O-DR) were used. Vasomotor responses to electrical field stimulation (EFS), NA and the NO donor DEA-NO were studied. The expressions of neuronal NOS (nNOS) and phospho-nNOS (P-nNOS) and release of NA, ATP and NO were determined. Sympathetic and nitrergic nerve densities were analysed by immunofluorescence.

Key results: Blood pressure was higher in O-DR animals. EFS-induced vasoconstriction was greater in O-DR animals. This response was decreased by phentolamine more in O-DR animals than their controls. L-NAME increased EFS-induced vasoconstriction more strongly in O-DR than in O-CR segments. Vasomotor responses to NA or DEA-NO were not modified. NA, ATP and NO release was increased in segments from O-DR. nNOS expression was not modified, whereas P-nNOS expression was increased in O-DR. Sympathetic and nitrergic nerve densities were similar in both experimental groups.

Conclusions and implications: The activity of sympathetic and nitrergic innervation is increased in SMA from O-DR animals. The net effect is an increase in EFS-induced contractions in these animals. These effects may contribute to the increased blood pressure observed in the offspring of diabetic rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Adenosine Triphosphate / metabolism
  • Animals
  • Blood Glucose / analysis
  • Blood Pressure
  • Body Weight
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology*
  • Electric Stimulation
  • Female
  • Male
  • Mesenteric Arteries / innervation*
  • Mesenteric Arteries / metabolism
  • Mesenteric Arteries / physiopathology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type I / metabolism
  • Pregnancy
  • Rats, Wistar
  • Sodium / metabolism
  • Superoxides / metabolism
  • Vasoconstriction
  • Vasodilation

Substances

  • Blood Glucose
  • Superoxides
  • Nitric Oxide
  • Adenosine Triphosphate
  • Sodium
  • Nitric Oxide Synthase Type I
  • Acetylcholine