Effects of diabetes and treatment with the antioxidant alpha-lipoic acid on endothelial and neurogenic responses of corpus cavernosum in rats

A Keegan, M A Cotter, Norman E Cameron

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Diabetes mellitus is associated with impotence in animal models and patients. Raised reactive oxygen species contribute to diabetic neurovascular deficits, which are amenable to antioxidant treatment. Our aim was to examine the effects of streptozotocin-induced diabetes in rats and long-term treatment with the antioxidant, alpha-lipoic acid: on responses of an in vitro corpus cavernosum preparation. Diabetes duration was 8 weeks and preventive and reversal (4 weeks untreated diabetes, 4 weeks of treatment) studies were done. Four and 8 weeks of diabetes caused an about 41 % reduction in endothelium-dependent nitric oxide mediated relaxation to acetylcholine in phenylephrine-precontracted cavernosum. This deficit was prevented (93.9 +/- 7.1 %) by treatment with alpha-lipoic acid; reversal studies showed 64.9 +/- 19.5 % correction. Neither diabetes nor treatment with alpha-lipoic acid altered endothelium-independent relaxation to the nitric oxide donor, sodium nitroprusside. Stimulation of corpus cavernosum autonomic innervation caused noradrenergic-mediated contractions that were unaffected by diabetes or alpha-lipoic acid. Non-adrenergic, non-cholinergic nerve responses, largely dependent on nitric oxide, were seen after phenylephrine precontraction in the presence of atropine and guanethidine. Non-adrenergic, non-cholinergic stimulation caused frequency dependent relaxation to a maximum of about 40 %. Diabetes reduced this to about 25 %, however with preventive alpha-lipoic acid treatment, non-adrenergic, noncholinergic relaxation was in the nondiabetic range. In the reversal alpha-lipoic acid treated diabetic group, its deficit was corrected by 52.1 +/- 14.6%. Thus, diabetes reduces endothelium and non-adrenergic, noncholinergic nerve nitric oxide-mediated relaxation of corpus cavernosum smooth muscle, which is likely to be the organic base for impotence. Prevention and partial correction by alpha-lipoic acid emphasises the importance of reactive oxygen species and suggests a potential therapeutic approach.

Original languageEnglish
Pages (from-to)343-350
Number of pages8
JournalDiabetologia
Volume42
Publication statusPublished - 1999

Keywords

  • diabetes mellitus
  • corpus cavernosum
  • autonomic neuropathy
  • antioxidant
  • nitric oxide
  • impotence
  • rat
  • NITRIC-OXIDE SYNTHASE
  • VASOACTIVE INTESTINAL POLYPEPTIDE
  • PROTEIN-KINASE-C
  • DEPENDENT RELAXATION
  • SMOOTH-MUSCLE
  • FREE-RADICALS
  • SUPEROXIDE-DISMUTASE
  • SELECTIVE IMPAIRMENT
  • RESISTANCE ARTERIES
  • INDUCED ACTIVATION

Cite this

Effects of diabetes and treatment with the antioxidant alpha-lipoic acid on endothelial and neurogenic responses of corpus cavernosum in rats. / Keegan, A ; Cotter, M A ; Cameron, Norman E.

In: Diabetologia, Vol. 42, 1999, p. 343-350.

Research output: Contribution to journalArticle

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T1 - Effects of diabetes and treatment with the antioxidant alpha-lipoic acid on endothelial and neurogenic responses of corpus cavernosum in rats

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AU - Cotter, M A

AU - Cameron, Norman E

PY - 1999

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N2 - Diabetes mellitus is associated with impotence in animal models and patients. Raised reactive oxygen species contribute to diabetic neurovascular deficits, which are amenable to antioxidant treatment. Our aim was to examine the effects of streptozotocin-induced diabetes in rats and long-term treatment with the antioxidant, alpha-lipoic acid: on responses of an in vitro corpus cavernosum preparation. Diabetes duration was 8 weeks and preventive and reversal (4 weeks untreated diabetes, 4 weeks of treatment) studies were done. Four and 8 weeks of diabetes caused an about 41 % reduction in endothelium-dependent nitric oxide mediated relaxation to acetylcholine in phenylephrine-precontracted cavernosum. This deficit was prevented (93.9 +/- 7.1 %) by treatment with alpha-lipoic acid; reversal studies showed 64.9 +/- 19.5 % correction. Neither diabetes nor treatment with alpha-lipoic acid altered endothelium-independent relaxation to the nitric oxide donor, sodium nitroprusside. Stimulation of corpus cavernosum autonomic innervation caused noradrenergic-mediated contractions that were unaffected by diabetes or alpha-lipoic acid. Non-adrenergic, non-cholinergic nerve responses, largely dependent on nitric oxide, were seen after phenylephrine precontraction in the presence of atropine and guanethidine. Non-adrenergic, non-cholinergic stimulation caused frequency dependent relaxation to a maximum of about 40 %. Diabetes reduced this to about 25 %, however with preventive alpha-lipoic acid treatment, non-adrenergic, noncholinergic relaxation was in the nondiabetic range. In the reversal alpha-lipoic acid treated diabetic group, its deficit was corrected by 52.1 +/- 14.6%. Thus, diabetes reduces endothelium and non-adrenergic, noncholinergic nerve nitric oxide-mediated relaxation of corpus cavernosum smooth muscle, which is likely to be the organic base for impotence. Prevention and partial correction by alpha-lipoic acid emphasises the importance of reactive oxygen species and suggests a potential therapeutic approach.

AB - Diabetes mellitus is associated with impotence in animal models and patients. Raised reactive oxygen species contribute to diabetic neurovascular deficits, which are amenable to antioxidant treatment. Our aim was to examine the effects of streptozotocin-induced diabetes in rats and long-term treatment with the antioxidant, alpha-lipoic acid: on responses of an in vitro corpus cavernosum preparation. Diabetes duration was 8 weeks and preventive and reversal (4 weeks untreated diabetes, 4 weeks of treatment) studies were done. Four and 8 weeks of diabetes caused an about 41 % reduction in endothelium-dependent nitric oxide mediated relaxation to acetylcholine in phenylephrine-precontracted cavernosum. This deficit was prevented (93.9 +/- 7.1 %) by treatment with alpha-lipoic acid; reversal studies showed 64.9 +/- 19.5 % correction. Neither diabetes nor treatment with alpha-lipoic acid altered endothelium-independent relaxation to the nitric oxide donor, sodium nitroprusside. Stimulation of corpus cavernosum autonomic innervation caused noradrenergic-mediated contractions that were unaffected by diabetes or alpha-lipoic acid. Non-adrenergic, non-cholinergic nerve responses, largely dependent on nitric oxide, were seen after phenylephrine precontraction in the presence of atropine and guanethidine. Non-adrenergic, non-cholinergic stimulation caused frequency dependent relaxation to a maximum of about 40 %. Diabetes reduced this to about 25 %, however with preventive alpha-lipoic acid treatment, non-adrenergic, noncholinergic relaxation was in the nondiabetic range. In the reversal alpha-lipoic acid treated diabetic group, its deficit was corrected by 52.1 +/- 14.6%. Thus, diabetes reduces endothelium and non-adrenergic, noncholinergic nerve nitric oxide-mediated relaxation of corpus cavernosum smooth muscle, which is likely to be the organic base for impotence. Prevention and partial correction by alpha-lipoic acid emphasises the importance of reactive oxygen species and suggests a potential therapeutic approach.

KW - diabetes mellitus

KW - corpus cavernosum

KW - autonomic neuropathy

KW - antioxidant

KW - nitric oxide

KW - impotence

KW - rat

KW - NITRIC-OXIDE SYNTHASE

KW - VASOACTIVE INTESTINAL POLYPEPTIDE

KW - PROTEIN-KINASE-C

KW - DEPENDENT RELAXATION

KW - SMOOTH-MUSCLE

KW - FREE-RADICALS

KW - SUPEROXIDE-DISMUTASE

KW - SELECTIVE IMPAIRMENT

KW - RESISTANCE ARTERIES

KW - INDUCED ACTIVATION

M3 - Article

VL - 42

SP - 343

EP - 350

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

ER -