The role of the renin-angiotensin system and oxidative stress in spontaneously hypertensive rat mesenteric collateral growth impairment

Steven J. Miller, Laura E. Norton, Michael P. Murphy, Michael C. Dalsing, Joseph L. Unthank

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Abstract

Recent clinical and animal studies have shown that collateral artery growth is impaired in the presence of vascular risk factors, including hypertension. Available evidence suggests that angiotensin-converting enzyme inhibitors (ACEI) promote collateral growth in both hypertensive humans and animals; however, the specific mechanisms are not established. This study evaluated the hypothesis that collateral growth impairment in hypertension is mediated by excess superoxide produced by NAD(P)H oxidase in response to stimulation of the ANG II type 1 receptor. After ileal artery ligation, mesenteric collateral growth did not occur in untreated, young, spontaneously hypertensive rats. Significant luminal expansion occurred in collaterals of spontaneously hypertensive rats treated with the superoxide dismutase mimetic tempol, the NAD(P)H oxidase inhibitor apocynin, and the ACEI captopril, but not ANG II type 1 (losartan) or type 2 (PD-123319) receptor blockers. The ACEI enalapril produced equivalent reduction of arterial pressure as captopril but did not promote luminal expansion. This suggests the effects of captopril on collateral growth might result from its antioxidant properties. RT-PCR demonstrated that ANG II type 1 receptor and angiotensinogen expression was reduced in collaterals of untreated rats. This local suppression of the renin angiotensin system provides a potential explanation for the lack of effect of enalapril and losartan on collateral growth. The results demonstrate the capability of antioxidant therapies, including captopril, to reverse impaired collateral artery growth and the novel finding that components of the local renin angiotensin system are naturally suppressed in collaterals.

Original languageEnglish (US)
Pages (from-to)H2523-H2531
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number5
DOIs
StatePublished - May 1 2007

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Keywords

  • Angiotensin-converting enzyme inhibitor
  • Antioxidant
  • Arteriogenesis
  • Captopril
  • Collateral growth
  • Hypertension

ASJC Scopus subject areas

  • Physiology

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