Effects of diabetes and evening primrose oil treatment on responses of aorta, corpus cavernosum and mesenteric vasculature in rats

Alison Margaret Jack, A. Keegan, Mary Anne Cotter, Norman E Cameron

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Abstract

Diabetes causes endothelial dysfunction, with deleterious effects on nitric oxide (NO) mediated vasodilatation. However, in many vessels other local vasodilators such as endothelium-derived hyperpolarizing factor (EDHF), prostacyclin, epoxides or endocannabinoids are also important. Several of these factors may be derived from omega-6 essential fatty acids via arachidonate metabolism. Diabetes inhibits this pathway, a defect that may be bypassed by diets enriched with w-6 gamma-linolenic acid-containing oils such as evening primrose oil (EPO). The aim was to examine the effects of preventive EPO treatment on endothelium-dependent and neurally mediated vasorelaxation. Diabetes was induced by streptozotocin in rats; duration was 8 weeks. Vascular responses were examined in vitro on thoracic aorta, corpus cavernosum and perfused mesenteric bed preparations. Diabetes caused 25% and 35% deficits, respectively, in aorta and corpus cavernosum NO-mediated endothelium-dependent relaxation to acetylcholine that were largely unaffected by EPO treatment. Moreover, a 44% reduction in maximum corpus cavernosum vasorelaxation to nitrergic nerve stimulation was not prevented by EPO. However, for the mesenteric vascular bed, a 29% diminution of responses to acetylcholine, mediated by both NO and EDHF, was 84% attenuated by EPO treatment. When the EDHF component was isolated during NO synthase inhibition, a 76% diabetic deficit was noted. This was completely prevented by EPO treatment, which also caused supernormal EDHF responses in nondiabetic rats. EPO treatment prevented the development of deficits in endothelium-dependent relaxation in diabetic rats. Effects were particularly marked on the resistance vessel EDHF system, which may have potential therapeutic relevance for diabetic microvascular complications. (C) 2002 Elsevier Science Inc. All rights reserved.

Original languageEnglish
Pages (from-to)1863-1877
Number of pages14
JournalLife Sciences
Volume71
Issue number16
DOIs
Publication statusPublished - 2002

Keywords

  • diabetes
  • endothelial function
  • lipid metabolism
  • nitric oxide
  • EDHF
  • corpus cavernosum
  • GAMMA-LINOLENIC ACID
  • ALPHA-LIPOIC ACID
  • ENDOTHELIUM-DEPENDENT HYPERPOLARIZATION
  • ALDOSE REDUCTASE INHIBITION
  • PORCINE CORONARY-ARTERIES
  • NITRIC-OXIDE PRODUCTION
  • ESSENTIAL FATTY-ACIDS
  • DIETARY SUPPLEMENTATION
  • ARACHIDONIC-ACID
  • POLYOL PATHWAY

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