Effects of rosuvastatin on nitric oxide-dependent function in aorta and corpus cavernosum of diabetic mice: relationship to cholesterol biosynthesis pathway inhibition and lipid lowering

Matthew Robert Nangle, Mary Anne Cotter, Norman E Cameron

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Elevated plasma lipids contribute to neurovascular dysfunction in diabetes. Statins have lipid-lowering properties and can modulate endothelial nitric oxide (NO) bioavailability. The aim was to assess the impact of these factors on autonomic nitrergic nerve and endothelial function. Thus, the effects of diabetes and treatment with the HMG-CoA reductase inhibitor rosuvastatin (RSV) were examined on corpus cavernosum and aorta from streptozotocin-induced diabetic mice in a 4-week prevention study and a 2-week intervention study, following 4 weeks of untreated diabetes. Cotreatment with mevalonate was used to assess the dependence of RSV's effects on HMG-CoA reductase blockade. Diabetes caused a 25% reduction in NO-mediated endothelium-dependent relaxation to acetylcholine for aorta and cavernosum. Relaxations of cavernosum were in the nondiabetic range following prevention or reversal treatment. The aortic deficit was completely prevented and 60% reversed by RSV. Maximum NO-dependent nonadrenergic, noncholinergic nerve-mediated relaxations of cavernosum were reduced 25-33% by diabetes. RSV treatment prevented 75% and reversed 71% of this diabetic deficit. Cotreatment with mevalonate inhibited the beneficial actions of RSV on aorta and cavernosum. Total plasma cholesterol was unaltered by diabetes or treatment. Thus, RSV corrected defective NO-mediated nerve and vascular function in diabetic mice independent of cholesterol lowering but via effects dependent on cholesterol biosynthesis pathway inhibition.

Original languageEnglish
Pages (from-to)2396-2402
Number of pages6
JournalDiabetes
Volume52
Issue number9
DOIs
Publication statusPublished - Sep 2003

Keywords

  • COA REDUCTASE INHIBITOR
  • ENDOTHELIAL-CELLS
  • VITAMIN-E
  • 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE
  • STATIN THERAPY
  • SMOOTH-MUSCLE
  • SYNTHASE
  • RELAXATION
  • ATHEROSCLEROSIS
  • EXPRESSION

Cite this

Effects of rosuvastatin on nitric oxide-dependent function in aorta and corpus cavernosum of diabetic mice: relationship to cholesterol biosynthesis pathway inhibition and lipid lowering. / Nangle, Matthew Robert; Cotter, Mary Anne; Cameron, Norman E.

In: Diabetes, Vol. 52, No. 9, 09.2003, p. 2396-2402.

Research output: Contribution to journalArticle

@article{d99f84a912b54450b409b7c77ec0d463,
title = "Effects of rosuvastatin on nitric oxide-dependent function in aorta and corpus cavernosum of diabetic mice: relationship to cholesterol biosynthesis pathway inhibition and lipid lowering",
abstract = "Elevated plasma lipids contribute to neurovascular dysfunction in diabetes. Statins have lipid-lowering properties and can modulate endothelial nitric oxide (NO) bioavailability. The aim was to assess the impact of these factors on autonomic nitrergic nerve and endothelial function. Thus, the effects of diabetes and treatment with the HMG-CoA reductase inhibitor rosuvastatin (RSV) were examined on corpus cavernosum and aorta from streptozotocin-induced diabetic mice in a 4-week prevention study and a 2-week intervention study, following 4 weeks of untreated diabetes. Cotreatment with mevalonate was used to assess the dependence of RSV's effects on HMG-CoA reductase blockade. Diabetes caused a 25{\%} reduction in NO-mediated endothelium-dependent relaxation to acetylcholine for aorta and cavernosum. Relaxations of cavernosum were in the nondiabetic range following prevention or reversal treatment. The aortic deficit was completely prevented and 60{\%} reversed by RSV. Maximum NO-dependent nonadrenergic, noncholinergic nerve-mediated relaxations of cavernosum were reduced 25-33{\%} by diabetes. RSV treatment prevented 75{\%} and reversed 71{\%} of this diabetic deficit. Cotreatment with mevalonate inhibited the beneficial actions of RSV on aorta and cavernosum. Total plasma cholesterol was unaltered by diabetes or treatment. Thus, RSV corrected defective NO-mediated nerve and vascular function in diabetic mice independent of cholesterol lowering but via effects dependent on cholesterol biosynthesis pathway inhibition.",
keywords = "COA REDUCTASE INHIBITOR, ENDOTHELIAL-CELLS, VITAMIN-E, 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE, STATIN THERAPY, SMOOTH-MUSCLE, SYNTHASE, RELAXATION, ATHEROSCLEROSIS, EXPRESSION",
author = "Nangle, {Matthew Robert} and Cotter, {Mary Anne} and Cameron, {Norman E}",
year = "2003",
month = "9",
doi = "10.2337/DIABETES.52.9.2396",
language = "English",
volume = "52",
pages = "2396--2402",
journal = "Diabetes",
issn = "0012-1797",
publisher = "AMER DIABETES ASSOC",
number = "9",

}

TY - JOUR

T1 - Effects of rosuvastatin on nitric oxide-dependent function in aorta and corpus cavernosum of diabetic mice: relationship to cholesterol biosynthesis pathway inhibition and lipid lowering

AU - Nangle, Matthew Robert

AU - Cotter, Mary Anne

AU - Cameron, Norman E

PY - 2003/9

Y1 - 2003/9

N2 - Elevated plasma lipids contribute to neurovascular dysfunction in diabetes. Statins have lipid-lowering properties and can modulate endothelial nitric oxide (NO) bioavailability. The aim was to assess the impact of these factors on autonomic nitrergic nerve and endothelial function. Thus, the effects of diabetes and treatment with the HMG-CoA reductase inhibitor rosuvastatin (RSV) were examined on corpus cavernosum and aorta from streptozotocin-induced diabetic mice in a 4-week prevention study and a 2-week intervention study, following 4 weeks of untreated diabetes. Cotreatment with mevalonate was used to assess the dependence of RSV's effects on HMG-CoA reductase blockade. Diabetes caused a 25% reduction in NO-mediated endothelium-dependent relaxation to acetylcholine for aorta and cavernosum. Relaxations of cavernosum were in the nondiabetic range following prevention or reversal treatment. The aortic deficit was completely prevented and 60% reversed by RSV. Maximum NO-dependent nonadrenergic, noncholinergic nerve-mediated relaxations of cavernosum were reduced 25-33% by diabetes. RSV treatment prevented 75% and reversed 71% of this diabetic deficit. Cotreatment with mevalonate inhibited the beneficial actions of RSV on aorta and cavernosum. Total plasma cholesterol was unaltered by diabetes or treatment. Thus, RSV corrected defective NO-mediated nerve and vascular function in diabetic mice independent of cholesterol lowering but via effects dependent on cholesterol biosynthesis pathway inhibition.

AB - Elevated plasma lipids contribute to neurovascular dysfunction in diabetes. Statins have lipid-lowering properties and can modulate endothelial nitric oxide (NO) bioavailability. The aim was to assess the impact of these factors on autonomic nitrergic nerve and endothelial function. Thus, the effects of diabetes and treatment with the HMG-CoA reductase inhibitor rosuvastatin (RSV) were examined on corpus cavernosum and aorta from streptozotocin-induced diabetic mice in a 4-week prevention study and a 2-week intervention study, following 4 weeks of untreated diabetes. Cotreatment with mevalonate was used to assess the dependence of RSV's effects on HMG-CoA reductase blockade. Diabetes caused a 25% reduction in NO-mediated endothelium-dependent relaxation to acetylcholine for aorta and cavernosum. Relaxations of cavernosum were in the nondiabetic range following prevention or reversal treatment. The aortic deficit was completely prevented and 60% reversed by RSV. Maximum NO-dependent nonadrenergic, noncholinergic nerve-mediated relaxations of cavernosum were reduced 25-33% by diabetes. RSV treatment prevented 75% and reversed 71% of this diabetic deficit. Cotreatment with mevalonate inhibited the beneficial actions of RSV on aorta and cavernosum. Total plasma cholesterol was unaltered by diabetes or treatment. Thus, RSV corrected defective NO-mediated nerve and vascular function in diabetic mice independent of cholesterol lowering but via effects dependent on cholesterol biosynthesis pathway inhibition.

KW - COA REDUCTASE INHIBITOR

KW - ENDOTHELIAL-CELLS

KW - VITAMIN-E

KW - 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE

KW - STATIN THERAPY

KW - SMOOTH-MUSCLE

KW - SYNTHASE

KW - RELAXATION

KW - ATHEROSCLEROSIS

KW - EXPRESSION

U2 - 10.2337/DIABETES.52.9.2396

DO - 10.2337/DIABETES.52.9.2396

M3 - Article

VL - 52

SP - 2396

EP - 2402

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 9

ER -