Correction of nitrergic neurovascular dysfunction in diabetic mouse corpus cavernosum by p38 mitogen-activated protein kinase inhibition

M R Nangle, M A Cotter, Norman E Cameron

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Increased p38 mitogen-activated protein kinase ( MAPK) in response to stress stimuli, including hyperglycemia, contributes to diabetic somatic neuropathy. However, effects on autonomic nerve and vascular function have not been determined. The aim of this study was to investigate the effects of the p38 MAPK inhibitor, LY2161793, on penile neurovascular function in streptozotocin-induced diabetic mice. Diabetes duration was 6 weeks and intervention LY2161793 treatment was given for the final 2 weeks. In vitro measurements on phenylephrine-precontracted corpus cavernosum revealed a 32% reduction in maximum nitrergic nerve-mediated relaxation with diabetes that was 74% corrected by LY2161793 treatment. Maximum nitric oxide-mediated endothelium-dependent relaxation to acetylcholine was 42% attenuated by diabetes and 88% restored by LY2161793. Moreover, treatment partially corrected a diabetic deficit in endothelium-independent relaxation to a nitric oxide donor. Thus, p38 MAPK inhibition corrects nitric oxide-dependent indices of diabetic erectile autonomic neuropathy and vasculopathy, a therapeutic approach potentially worthy of consideration for clinical trials.

Original languageEnglish
Pages (from-to)258-263
Number of pages6
JournalInternational Journal of Impotence Research
Volume18
DOIs
Publication statusPublished - 2006

Keywords

  • corpus cavernosum
  • diabetes
  • endothelium
  • neuropathy
  • nitric oxide
  • p38 mitogen-activated protein kinase
  • smooth muscle
  • ALPHA-LIPOIC ACID
  • SMOOTH-MUSCLE
  • MAP KINASE
  • ENDOTHELIAL DYSFUNCTION
  • RATS
  • RELAXATION
  • GLUCOSE
  • MICE
  • NEUROPATHY
  • MELLITUS

Cite this

Correction of nitrergic neurovascular dysfunction in diabetic mouse corpus cavernosum by p38 mitogen-activated protein kinase inhibition. / Nangle, M R ; Cotter, M A ; Cameron, Norman E.

In: International Journal of Impotence Research, Vol. 18, 2006, p. 258-263.

Research output: Contribution to journalArticle

@article{cc40a34f1e0f433fa6aa95d8562d09d1,
title = "Correction of nitrergic neurovascular dysfunction in diabetic mouse corpus cavernosum by p38 mitogen-activated protein kinase inhibition",
abstract = "Increased p38 mitogen-activated protein kinase ( MAPK) in response to stress stimuli, including hyperglycemia, contributes to diabetic somatic neuropathy. However, effects on autonomic nerve and vascular function have not been determined. The aim of this study was to investigate the effects of the p38 MAPK inhibitor, LY2161793, on penile neurovascular function in streptozotocin-induced diabetic mice. Diabetes duration was 6 weeks and intervention LY2161793 treatment was given for the final 2 weeks. In vitro measurements on phenylephrine-precontracted corpus cavernosum revealed a 32{\%} reduction in maximum nitrergic nerve-mediated relaxation with diabetes that was 74{\%} corrected by LY2161793 treatment. Maximum nitric oxide-mediated endothelium-dependent relaxation to acetylcholine was 42{\%} attenuated by diabetes and 88{\%} restored by LY2161793. Moreover, treatment partially corrected a diabetic deficit in endothelium-independent relaxation to a nitric oxide donor. Thus, p38 MAPK inhibition corrects nitric oxide-dependent indices of diabetic erectile autonomic neuropathy and vasculopathy, a therapeutic approach potentially worthy of consideration for clinical trials.",
keywords = "corpus cavernosum, diabetes, endothelium, neuropathy, nitric oxide, p38 mitogen-activated protein kinase, smooth muscle, ALPHA-LIPOIC ACID, SMOOTH-MUSCLE, MAP KINASE, ENDOTHELIAL DYSFUNCTION, RATS, RELAXATION, GLUCOSE, MICE, NEUROPATHY, MELLITUS",
author = "Nangle, {M R} and Cotter, {M A} and Cameron, {Norman E}",
year = "2006",
doi = "10.1038/sj.ijir.3901414",
language = "English",
volume = "18",
pages = "258--263",
journal = "International Journal of Impotence Research",
issn = "0955-9930",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Correction of nitrergic neurovascular dysfunction in diabetic mouse corpus cavernosum by p38 mitogen-activated protein kinase inhibition

AU - Nangle, M R

AU - Cotter, M A

AU - Cameron, Norman E

PY - 2006

Y1 - 2006

N2 - Increased p38 mitogen-activated protein kinase ( MAPK) in response to stress stimuli, including hyperglycemia, contributes to diabetic somatic neuropathy. However, effects on autonomic nerve and vascular function have not been determined. The aim of this study was to investigate the effects of the p38 MAPK inhibitor, LY2161793, on penile neurovascular function in streptozotocin-induced diabetic mice. Diabetes duration was 6 weeks and intervention LY2161793 treatment was given for the final 2 weeks. In vitro measurements on phenylephrine-precontracted corpus cavernosum revealed a 32% reduction in maximum nitrergic nerve-mediated relaxation with diabetes that was 74% corrected by LY2161793 treatment. Maximum nitric oxide-mediated endothelium-dependent relaxation to acetylcholine was 42% attenuated by diabetes and 88% restored by LY2161793. Moreover, treatment partially corrected a diabetic deficit in endothelium-independent relaxation to a nitric oxide donor. Thus, p38 MAPK inhibition corrects nitric oxide-dependent indices of diabetic erectile autonomic neuropathy and vasculopathy, a therapeutic approach potentially worthy of consideration for clinical trials.

AB - Increased p38 mitogen-activated protein kinase ( MAPK) in response to stress stimuli, including hyperglycemia, contributes to diabetic somatic neuropathy. However, effects on autonomic nerve and vascular function have not been determined. The aim of this study was to investigate the effects of the p38 MAPK inhibitor, LY2161793, on penile neurovascular function in streptozotocin-induced diabetic mice. Diabetes duration was 6 weeks and intervention LY2161793 treatment was given for the final 2 weeks. In vitro measurements on phenylephrine-precontracted corpus cavernosum revealed a 32% reduction in maximum nitrergic nerve-mediated relaxation with diabetes that was 74% corrected by LY2161793 treatment. Maximum nitric oxide-mediated endothelium-dependent relaxation to acetylcholine was 42% attenuated by diabetes and 88% restored by LY2161793. Moreover, treatment partially corrected a diabetic deficit in endothelium-independent relaxation to a nitric oxide donor. Thus, p38 MAPK inhibition corrects nitric oxide-dependent indices of diabetic erectile autonomic neuropathy and vasculopathy, a therapeutic approach potentially worthy of consideration for clinical trials.

KW - corpus cavernosum

KW - diabetes

KW - endothelium

KW - neuropathy

KW - nitric oxide

KW - p38 mitogen-activated protein kinase

KW - smooth muscle

KW - ALPHA-LIPOIC ACID

KW - SMOOTH-MUSCLE

KW - MAP KINASE

KW - ENDOTHELIAL DYSFUNCTION

KW - RATS

KW - RELAXATION

KW - GLUCOSE

KW - MICE

KW - NEUROPATHY

KW - MELLITUS

U2 - 10.1038/sj.ijir.3901414

DO - 10.1038/sj.ijir.3901414

M3 - Article

VL - 18

SP - 258

EP - 263

JO - International Journal of Impotence Research

JF - International Journal of Impotence Research

SN - 0955-9930

ER -