Corpus cavernosum dysfunction in diabetic rats: effects of combined alpha-lipoic acid and gamma-linolenic acid treatment

A. Keegan, Mary Anne Cotter, Norman E Cameron

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Background The effects of streptozotocin-induced diabetes on nitric oxide (NO)-mediated relaxation of rat corpus cavernosum smooth muscle to: neurogenic and endothelial stimulation was examined. The aim was to assess the effects of treatment with low doses of the antioxidant, alpha -lipoic acid, and the omega -6 essential fatty acid, gamma -linolenic acid, either separately or in combination.

Methods Treatment was preventive from diabetes induction or corrective over 4 weeks after 4 weeks of untreated diabetes. Corpus cavenosum responses were examined in vitro.

Results Neither diabetes nor treatment affected contractile responses, to transmural electrical field stimulation of noradrenergic nerves. Stimulation of phenylephrine precontracted cavernosa in the presence of guanethidine and atropine caused relaxation via the nitrergic innervation. Maximum relaxation responses were 40% and 46% decreased after 4 and 8 weeks of diabetes, respectively. alpha -Lipoic acid, gamma -linolenic acid combination treatment fully prevented this deficit, and partially (52%) corrected the effect of 4 weeks, of untreated diabetes. Neither alpha -lipoic acid nor gamma -linolenic components alone had significant effects, which suggests that there were synergistic interactions between the drugs. Both 4 and 8 weeks of untreated diabetes reduced maximum endothelium-dependent relaxation of phenylephrine precontracted cavernosa to acetylcholine by approximately 40%. While alpha -lipoic acid or gamma -linolenic acid were ineffective, joint treatment fully prevented and corrected this diabetic endothelial deficit. Neither diabetes nor treatment affected endothelium-independent relaxation to the NO donor, sodium nitroprusside.

Conclusion The data show that alpha -lipoic acid and gamma -linolenic acid interact synergistically to improve NO-mediated neurogenic and endothelium-dependent relaxation of corpus cavernosum in experimental diabetes. Copyright (C) 2001 John Wiley & Sons, Ltd.

Original languageEnglish
Pages (from-to)380-386
Number of pages6
JournalDIABETES-METABOLISM RESEARCH AND REVIEWS
Volume17
Issue number5
DOIs
Publication statusPublished - 2001

Keywords

  • corpus cavernosum
  • autonomic neuropathy
  • non-adrenergic non-cholinergic innervation
  • antioxidant
  • essential fatty acid
  • nitric oxide
  • impotence
  • streptozotocin-diabetic rat
  • NITRIC-OXIDE SYNTHASE
  • SMOOTH-MUSCLE
  • BLOOD-FLOW
  • ENDOTHELIAL RELAXATION
  • ERECTILE DYSFUNCTION
  • PERIPHERAL-NERVE
  • OXIDATIVE STRESS
  • FREE-RADICALS
  • VITAMIN-E
  • NEUROPATHY

Cite this

Corpus cavernosum dysfunction in diabetic rats: effects of combined alpha-lipoic acid and gamma-linolenic acid treatment. / Keegan, A.; Cotter, Mary Anne; Cameron, Norman E.

In: DIABETES-METABOLISM RESEARCH AND REVIEWS, Vol. 17, No. 5, 2001, p. 380-386.

Research output: Contribution to journalArticle

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abstract = "Background The effects of streptozotocin-induced diabetes on nitric oxide (NO)-mediated relaxation of rat corpus cavernosum smooth muscle to: neurogenic and endothelial stimulation was examined. The aim was to assess the effects of treatment with low doses of the antioxidant, alpha -lipoic acid, and the omega -6 essential fatty acid, gamma -linolenic acid, either separately or in combination.Methods Treatment was preventive from diabetes induction or corrective over 4 weeks after 4 weeks of untreated diabetes. Corpus cavenosum responses were examined in vitro.Results Neither diabetes nor treatment affected contractile responses, to transmural electrical field stimulation of noradrenergic nerves. Stimulation of phenylephrine precontracted cavernosa in the presence of guanethidine and atropine caused relaxation via the nitrergic innervation. Maximum relaxation responses were 40{\%} and 46{\%} decreased after 4 and 8 weeks of diabetes, respectively. alpha -Lipoic acid, gamma -linolenic acid combination treatment fully prevented this deficit, and partially (52{\%}) corrected the effect of 4 weeks, of untreated diabetes. Neither alpha -lipoic acid nor gamma -linolenic components alone had significant effects, which suggests that there were synergistic interactions between the drugs. Both 4 and 8 weeks of untreated diabetes reduced maximum endothelium-dependent relaxation of phenylephrine precontracted cavernosa to acetylcholine by approximately 40{\%}. While alpha -lipoic acid or gamma -linolenic acid were ineffective, joint treatment fully prevented and corrected this diabetic endothelial deficit. Neither diabetes nor treatment affected endothelium-independent relaxation to the NO donor, sodium nitroprusside.Conclusion The data show that alpha -lipoic acid and gamma -linolenic acid interact synergistically to improve NO-mediated neurogenic and endothelium-dependent relaxation of corpus cavernosum in experimental diabetes. Copyright (C) 2001 John Wiley & Sons, Ltd.",
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T1 - Corpus cavernosum dysfunction in diabetic rats: effects of combined alpha-lipoic acid and gamma-linolenic acid treatment

AU - Keegan, A.

AU - Cotter, Mary Anne

AU - Cameron, Norman E

PY - 2001

Y1 - 2001

N2 - Background The effects of streptozotocin-induced diabetes on nitric oxide (NO)-mediated relaxation of rat corpus cavernosum smooth muscle to: neurogenic and endothelial stimulation was examined. The aim was to assess the effects of treatment with low doses of the antioxidant, alpha -lipoic acid, and the omega -6 essential fatty acid, gamma -linolenic acid, either separately or in combination.Methods Treatment was preventive from diabetes induction or corrective over 4 weeks after 4 weeks of untreated diabetes. Corpus cavenosum responses were examined in vitro.Results Neither diabetes nor treatment affected contractile responses, to transmural electrical field stimulation of noradrenergic nerves. Stimulation of phenylephrine precontracted cavernosa in the presence of guanethidine and atropine caused relaxation via the nitrergic innervation. Maximum relaxation responses were 40% and 46% decreased after 4 and 8 weeks of diabetes, respectively. alpha -Lipoic acid, gamma -linolenic acid combination treatment fully prevented this deficit, and partially (52%) corrected the effect of 4 weeks, of untreated diabetes. Neither alpha -lipoic acid nor gamma -linolenic components alone had significant effects, which suggests that there were synergistic interactions between the drugs. Both 4 and 8 weeks of untreated diabetes reduced maximum endothelium-dependent relaxation of phenylephrine precontracted cavernosa to acetylcholine by approximately 40%. While alpha -lipoic acid or gamma -linolenic acid were ineffective, joint treatment fully prevented and corrected this diabetic endothelial deficit. Neither diabetes nor treatment affected endothelium-independent relaxation to the NO donor, sodium nitroprusside.Conclusion The data show that alpha -lipoic acid and gamma -linolenic acid interact synergistically to improve NO-mediated neurogenic and endothelium-dependent relaxation of corpus cavernosum in experimental diabetes. Copyright (C) 2001 John Wiley & Sons, Ltd.

AB - Background The effects of streptozotocin-induced diabetes on nitric oxide (NO)-mediated relaxation of rat corpus cavernosum smooth muscle to: neurogenic and endothelial stimulation was examined. The aim was to assess the effects of treatment with low doses of the antioxidant, alpha -lipoic acid, and the omega -6 essential fatty acid, gamma -linolenic acid, either separately or in combination.Methods Treatment was preventive from diabetes induction or corrective over 4 weeks after 4 weeks of untreated diabetes. Corpus cavenosum responses were examined in vitro.Results Neither diabetes nor treatment affected contractile responses, to transmural electrical field stimulation of noradrenergic nerves. Stimulation of phenylephrine precontracted cavernosa in the presence of guanethidine and atropine caused relaxation via the nitrergic innervation. Maximum relaxation responses were 40% and 46% decreased after 4 and 8 weeks of diabetes, respectively. alpha -Lipoic acid, gamma -linolenic acid combination treatment fully prevented this deficit, and partially (52%) corrected the effect of 4 weeks, of untreated diabetes. Neither alpha -lipoic acid nor gamma -linolenic components alone had significant effects, which suggests that there were synergistic interactions between the drugs. Both 4 and 8 weeks of untreated diabetes reduced maximum endothelium-dependent relaxation of phenylephrine precontracted cavernosa to acetylcholine by approximately 40%. While alpha -lipoic acid or gamma -linolenic acid were ineffective, joint treatment fully prevented and corrected this diabetic endothelial deficit. Neither diabetes nor treatment affected endothelium-independent relaxation to the NO donor, sodium nitroprusside.Conclusion The data show that alpha -lipoic acid and gamma -linolenic acid interact synergistically to improve NO-mediated neurogenic and endothelium-dependent relaxation of corpus cavernosum in experimental diabetes. Copyright (C) 2001 John Wiley & Sons, Ltd.

KW - corpus cavernosum

KW - autonomic neuropathy

KW - non-adrenergic non-cholinergic innervation

KW - antioxidant

KW - essential fatty acid

KW - nitric oxide

KW - impotence

KW - streptozotocin-diabetic rat

KW - NITRIC-OXIDE SYNTHASE

KW - SMOOTH-MUSCLE

KW - BLOOD-FLOW

KW - ENDOTHELIAL RELAXATION

KW - ERECTILE DYSFUNCTION

KW - PERIPHERAL-NERVE

KW - OXIDATIVE STRESS

KW - FREE-RADICALS

KW - VITAMIN-E

KW - NEUROPATHY

U2 - 10.1002/dmrr.215

DO - 10.1002/dmrr.215

M3 - Article

VL - 17

SP - 380

EP - 386

JO - DIABETES-METABOLISM RESEARCH AND REVIEWS

JF - DIABETES-METABOLISM RESEARCH AND REVIEWS

SN - 1520-7552

IS - 5

ER -