Sex-specific vascular responses of the rat aorta: effects of moderate term (intermediate stage) streptozotocin-induced diabetes

Can J Physiol Pharmacol. 2016 Apr;94(4):408-15. doi: 10.1139/cjpp-2015-0272. Epub 2015 Sep 17.

Abstract

Hyperglycemia affects male and female vascular beds differently. We have previously shown that 1 week after the induction of diabetes with streptozotocin (STZ), male and female rats exhibit differences in aortic endothelial function. To examine this phenomenon further, aortic responses were studied in male and female rats 8 weeks after the induction of diabetes (intermediate stage). Endothelium-dependent vasodilation (EDV) to acetylcholine (ACh) was measured in phenylephrine (PE) pre-contracted rat aortic rings. Concentration response curves to PE were generated before and after L-NAME, a nitric oxide synthase (NOS) inhibitor. Furthermore, mRNA expression of endothelial nitric oxide synthase (eNOS) and NADPH oxidase subunit (Nox1) were determined. At 8 weeks, diabetes impaired EDV to a greater extent in female than male aortae. Furthermore, the responsiveness to PE was significantly enhanced only in female diabetic rats, and basal NO, as indicated by the potentiation of the response to PE after L-NAME, was reduced in female diabetic rat aortae to the same levels as in males. In addition, eNOS mRNA expression was decreased, while the Nox1 expression was significantly enhanced in diabetic female rats. These results suggest that aortic function in female diabetic rats after 8 weeks exhibits a more prominent impairment and that NO may be involved.

Keywords: aorte de rat; diabetes; diabète; différences entre les sexes; endothelial function; fonction endothéliale; nitric oxide; oxyde nitrique; rat aorta; sex differences; streptozotocin (STZ); streptozotocine (STZ).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Aorta / drug effects*
  • Aorta / metabolism
  • Aorta, Thoracic / drug effects*
  • Aorta, Thoracic / metabolism
  • Diabetes Mellitus, Experimental / chemically induced*
  • Diabetes Mellitus, Experimental / metabolism*
  • Endothelium, Vascular / drug effects*
  • Female
  • Male
  • NADH, NADPH Oxidoreductases / metabolism
  • NADPH Oxidase 1
  • NADPH Oxidases / metabolism
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Phenylephrine / pharmacology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin / pharmacology*
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology

Substances

  • RNA, Messenger
  • Vasodilator Agents
  • Phenylephrine
  • Nitric Oxide
  • Streptozocin
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • NADH, NADPH Oxidoreductases
  • NADPH Oxidase 1
  • NADPH Oxidases
  • NOX1 protein, rat
  • Acetylcholine
  • NG-Nitroarginine Methyl Ester