Effects of spironolactone on cerebral vessel structure in rats with sustained hypertension

Christiné S. Rigsby, Adviye Ergul, Vera Portik Dobos, David M. Pollock, Anne M. Dorrance

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background Spironolactone prevents eutrophic middle cerebral artery (MCA) remodeling in young stroke-prone spontaneously hypertensive rats (SHRSP). Clinically, it is more relevant to identify treatments that improve vessel structure after hypertension and remodeling has developed. We hypothesized that spironolactone would increase the MCA lumen diameter and reduce the wall/lumen ratio in SHRSP treated from 12 to 18 weeks of age. Methods Twelve-week-old male SHRSP were treated with spironolactone (SHRSP spir 25mg/kg/day) for 6 weeks and were compared at 18 weeks to age matched untreated SHRSP and Wistar Kyoto (WKY) rats. MCA structure was assessed by pressure myography. The WKY rats were included to provide an indication of the magnitude of the hypertensive MCA remodeling. Results Spironolactone had no effect on blood pressure as measured by telemetry. MCA myogenic tone was enhanced in the SHRSP spir. Spironolactone increased the MCA lumen diameter (SHRSP 223.3± 9.7μm, SHRSP spir 283.7± 10.1μm, WKY 319.5± 8.8μm, analysis of variance (ANOVA) P <0.05) and reduced the wall/lumen ratio (SHRSP 0.107 ±0.007, SHRSP spir 0.078 ±0.006, WKY 0.047± 0.002, ANOVA P <0.05). Vessel wall stiffness was unchanged by spironolactone. Collagen 1 and 4 mRNA expression was increased in cerebral vessels from SHRSP compared to WKY rats; collagen 1 was reduced by spironolactone. Western blot analysis showed that active matrix metalloproteinase (MMP)-13 expression was increased by spironolactone treatment. The expression of intercellular adhesion molecule 1 (ICAM-1), a marker of inflammation, was increased in SHRSP and reduced by spironolactone. Conclusions These studies provide evidence that chronic mineralocorticoid receptor (MR) antagonism improves cerebral vessel structure after remodeling has developed in a model of human essential hypertension.

Original languageEnglish (US)
Pages (from-to)708-715
Number of pages8
JournalAmerican journal of hypertension
Volume24
Issue number6
DOIs
StatePublished - Jun 1 2011

Fingerprint

Spironolactone
Middle Cerebral Artery
Hypertension
Inbred WKY Rats
Analysis of Variance
Collagen
Myography
Matrix Metalloproteinase 13
Mineralocorticoid Receptors
Telemetry
Inbred SHR Rats
Intercellular Adhesion Molecule-1
Western Blotting
Stroke
Blood Pressure
Inflammation
Pressure
Messenger RNA

Keywords

  • SHRSP
  • arteriograph
  • blood pressure
  • hypertension
  • middle cerebral artery
  • spironolactone
  • vascular remodeling

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Rigsby, C. S., Ergul, A., Portik Dobos, V., Pollock, D. M., & Dorrance, A. M. (2011). Effects of spironolactone on cerebral vessel structure in rats with sustained hypertension. American journal of hypertension, 24(6), 708-715. https://doi.org/10.1038/ajh.2011.20

Effects of spironolactone on cerebral vessel structure in rats with sustained hypertension. / Rigsby, Christiné S.; Ergul, Adviye; Portik Dobos, Vera; Pollock, David M.; Dorrance, Anne M.

In: American journal of hypertension, Vol. 24, No. 6, 01.06.2011, p. 708-715.

Research output: Contribution to journalArticle

Rigsby, CS, Ergul, A, Portik Dobos, V, Pollock, DM & Dorrance, AM 2011, 'Effects of spironolactone on cerebral vessel structure in rats with sustained hypertension', American journal of hypertension, vol. 24, no. 6, pp. 708-715. https://doi.org/10.1038/ajh.2011.20
Rigsby, Christiné S. ; Ergul, Adviye ; Portik Dobos, Vera ; Pollock, David M. ; Dorrance, Anne M. / Effects of spironolactone on cerebral vessel structure in rats with sustained hypertension. In: American journal of hypertension. 2011 ; Vol. 24, No. 6. pp. 708-715.
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AU - Dorrance, Anne M.

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N2 - Background Spironolactone prevents eutrophic middle cerebral artery (MCA) remodeling in young stroke-prone spontaneously hypertensive rats (SHRSP). Clinically, it is more relevant to identify treatments that improve vessel structure after hypertension and remodeling has developed. We hypothesized that spironolactone would increase the MCA lumen diameter and reduce the wall/lumen ratio in SHRSP treated from 12 to 18 weeks of age. Methods Twelve-week-old male SHRSP were treated with spironolactone (SHRSP spir 25mg/kg/day) for 6 weeks and were compared at 18 weeks to age matched untreated SHRSP and Wistar Kyoto (WKY) rats. MCA structure was assessed by pressure myography. The WKY rats were included to provide an indication of the magnitude of the hypertensive MCA remodeling. Results Spironolactone had no effect on blood pressure as measured by telemetry. MCA myogenic tone was enhanced in the SHRSP spir. Spironolactone increased the MCA lumen diameter (SHRSP 223.3± 9.7μm, SHRSP spir 283.7± 10.1μm, WKY 319.5± 8.8μm, analysis of variance (ANOVA) P <0.05) and reduced the wall/lumen ratio (SHRSP 0.107 ±0.007, SHRSP spir 0.078 ±0.006, WKY 0.047± 0.002, ANOVA P <0.05). Vessel wall stiffness was unchanged by spironolactone. Collagen 1 and 4 mRNA expression was increased in cerebral vessels from SHRSP compared to WKY rats; collagen 1 was reduced by spironolactone. Western blot analysis showed that active matrix metalloproteinase (MMP)-13 expression was increased by spironolactone treatment. The expression of intercellular adhesion molecule 1 (ICAM-1), a marker of inflammation, was increased in SHRSP and reduced by spironolactone. Conclusions These studies provide evidence that chronic mineralocorticoid receptor (MR) antagonism improves cerebral vessel structure after remodeling has developed in a model of human essential hypertension.

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