Nitric oxide in experimental aneurysm formation: Early events and consequences of nitric oxide inhibition

Jason M. Johanning, Peter J. Armstrong, David P. Franklin, David Han, David J. Carey, James R. Elmore

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Mounting evidence suggests that nitric oxide (NO) plays an important role in aneurysm pathogenesis. Nitric oxide synthase (NOS) expression, hemodynamic consequences of NO inhibition, and the effect of NO on matrix metalloproteinase (MMP) expression during aneurysm formation are unknown. In this study, a standard intraaortic elastase infusion rat model was used. Control animals received intraaortic elastase infusion and intraperitoneal saline injections. Experimental groups received intraaortic elastase infusion and intraperitoneal injections of aminoguanidine (500 mg/kg) or L-NAME (2 mg/kg or 10 mg/kg). Aortic diameter, blood pressure, and NO metabolites were measured at surgery and postoperative (POD) 7. A second series of rats were randomly infused with intraaortic elastase or saline and aortas were analyzed on POD 1, 3, and 7 with Western blotting for iNOS, eNOS, and MMP-9 expression. Infusion of elastase produced aneurysms (p > 0.0001) in all rats. Inhibition of NO with aminoguanidine or L-NAME limited aneurysm expansion in all groups (p > 0.05). Nitric oxide metabolites were increased (p < 0.003) in control rats on POD 7. Arterial hypertension was present in all treated animals (p < 0.05). Early up-regulation on POD 1 of iNOS (p < 0.003) was noted in elastas-infused animals, but there was no iNOS expression with saline infusion. MMP-9 expression was present in both groups, with a significant increase in expression for elastase-infused animals noted on POD 7. iNOS expression is up-regulated early in experimental aneurysm formation, followed by increases in MMP-9 expression. Inhibition of NO limits aneurysmal expansion despite production of arterial hypertension.

Original languageEnglish (US)
Pages (from-to)65-72
Number of pages8
JournalAnnals of Vascular Surgery
Volume16
Issue number1
DOIs
StatePublished - Jan 1 2002

Fingerprint

Pancreatic Elastase
Aneurysm
Nitric Oxide
Matrix Metalloproteinase 9
NG-Nitroarginine Methyl Ester
Intraperitoneal Injections
Hypertension
Matrix Metalloproteinases
Nitric Oxide Synthase
Aorta
Arterial Pressure
Up-Regulation
Hemodynamics
Western Blotting

All Science Journal Classification (ASJC) codes

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

Johanning, Jason M. ; Armstrong, Peter J. ; Franklin, David P. ; Han, David ; Carey, David J. ; Elmore, James R. / Nitric oxide in experimental aneurysm formation : Early events and consequences of nitric oxide inhibition. In: Annals of Vascular Surgery. 2002 ; Vol. 16, No. 1. pp. 65-72.
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Nitric oxide in experimental aneurysm formation : Early events and consequences of nitric oxide inhibition. / Johanning, Jason M.; Armstrong, Peter J.; Franklin, David P.; Han, David; Carey, David J.; Elmore, James R.

In: Annals of Vascular Surgery, Vol. 16, No. 1, 01.01.2002, p. 65-72.

Research output: Contribution to journalArticle

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T1 - Nitric oxide in experimental aneurysm formation

T2 - Early events and consequences of nitric oxide inhibition

AU - Johanning, Jason M.

AU - Armstrong, Peter J.

AU - Franklin, David P.

AU - Han, David

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AU - Elmore, James R.

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N2 - Mounting evidence suggests that nitric oxide (NO) plays an important role in aneurysm pathogenesis. Nitric oxide synthase (NOS) expression, hemodynamic consequences of NO inhibition, and the effect of NO on matrix metalloproteinase (MMP) expression during aneurysm formation are unknown. In this study, a standard intraaortic elastase infusion rat model was used. Control animals received intraaortic elastase infusion and intraperitoneal saline injections. Experimental groups received intraaortic elastase infusion and intraperitoneal injections of aminoguanidine (500 mg/kg) or L-NAME (2 mg/kg or 10 mg/kg). Aortic diameter, blood pressure, and NO metabolites were measured at surgery and postoperative (POD) 7. A second series of rats were randomly infused with intraaortic elastase or saline and aortas were analyzed on POD 1, 3, and 7 with Western blotting for iNOS, eNOS, and MMP-9 expression. Infusion of elastase produced aneurysms (p > 0.0001) in all rats. Inhibition of NO with aminoguanidine or L-NAME limited aneurysm expansion in all groups (p > 0.05). Nitric oxide metabolites were increased (p < 0.003) in control rats on POD 7. Arterial hypertension was present in all treated animals (p < 0.05). Early up-regulation on POD 1 of iNOS (p < 0.003) was noted in elastas-infused animals, but there was no iNOS expression with saline infusion. MMP-9 expression was present in both groups, with a significant increase in expression for elastase-infused animals noted on POD 7. iNOS expression is up-regulated early in experimental aneurysm formation, followed by increases in MMP-9 expression. Inhibition of NO limits aneurysmal expansion despite production of arterial hypertension.

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