Preventing increased blood pressure in the obese Zucker rat improves severity of stroke

Jessica M. Osmond, James D. Mintz, David W Stepp

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Obesity is a risk factor for stroke, but the determinants of increased stroke risk in obesity are unknown. We have previously reported that obese Zucker rats (OZRs) have a worse stroke outcome and display evidence of remodeling of the middle cerebral artery (MCA), in parallel with hypertension, compared with lean controls. This study tested the hypothesis that hypertension is an essential determinant of cerebral vascular remodeling and increased stroke damage in OZRs. Blood pressure was measured by telemetery in lean and obese rats with and without hydrochlorthiazide (HCT; 2 mg·kg -1·day-1) from 8 to 15 wk of age. A separate group of rats was also chronically fed a low-sodium (LS) diet. Vessel structure was assessed in isolated, pressurized MCAs. Cerebral ischemia was induced for 60 min using an intralumenal suture technique, followed by 24 h of reperfusion. HCT treatment effectively prevented the increase in blood pressure in obese rats; however, the LS diet did not lower pressure. Importantly, infarct size was normalized by HCT after ischemia-reperfusion injury. Additionally, HCT improved the changes in MCA structure observed in untreated OZRs. There were no benefits of the LS diet on stroke injury or vessel structure. These results indicate that increased pressure is essential for driving the changes in infarct size in OZRs.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume299
Issue number1
DOIs
StatePublished - Jul 1 2010

Fingerprint

Zucker Rats
Sodium-Restricted Diet
Stroke
Blood Pressure
Middle Cerebral Artery
Obesity
Suture Techniques
Pressure
Reperfusion Injury
Brain Ischemia
Reperfusion
Hypertension
Wounds and Injuries

Keywords

  • Hydrochlorothiazide
  • Hypertension
  • Vascular remodeling

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Preventing increased blood pressure in the obese Zucker rat improves severity of stroke. / Osmond, Jessica M.; Mintz, James D.; Stepp, David W.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 299, No. 1, 01.07.2010.

Research output: Contribution to journalArticle

@article{d122e069e8cb41afbda7763f8eadcf00,
title = "Preventing increased blood pressure in the obese Zucker rat improves severity of stroke",
abstract = "Obesity is a risk factor for stroke, but the determinants of increased stroke risk in obesity are unknown. We have previously reported that obese Zucker rats (OZRs) have a worse stroke outcome and display evidence of remodeling of the middle cerebral artery (MCA), in parallel with hypertension, compared with lean controls. This study tested the hypothesis that hypertension is an essential determinant of cerebral vascular remodeling and increased stroke damage in OZRs. Blood pressure was measured by telemetery in lean and obese rats with and without hydrochlorthiazide (HCT; 2 mg·kg -1·day-1) from 8 to 15 wk of age. A separate group of rats was also chronically fed a low-sodium (LS) diet. Vessel structure was assessed in isolated, pressurized MCAs. Cerebral ischemia was induced for 60 min using an intralumenal suture technique, followed by 24 h of reperfusion. HCT treatment effectively prevented the increase in blood pressure in obese rats; however, the LS diet did not lower pressure. Importantly, infarct size was normalized by HCT after ischemia-reperfusion injury. Additionally, HCT improved the changes in MCA structure observed in untreated OZRs. There were no benefits of the LS diet on stroke injury or vessel structure. These results indicate that increased pressure is essential for driving the changes in infarct size in OZRs.",
keywords = "Hydrochlorothiazide, Hypertension, Vascular remodeling",
author = "Osmond, {Jessica M.} and Mintz, {James D.} and Stepp, {David W}",
year = "2010",
month = "7",
day = "1",
doi = "10.1152/ajpheart.01111.2009",
language = "English (US)",
volume = "299",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Preventing increased blood pressure in the obese Zucker rat improves severity of stroke

AU - Osmond, Jessica M.

AU - Mintz, James D.

AU - Stepp, David W

PY - 2010/7/1

Y1 - 2010/7/1

N2 - Obesity is a risk factor for stroke, but the determinants of increased stroke risk in obesity are unknown. We have previously reported that obese Zucker rats (OZRs) have a worse stroke outcome and display evidence of remodeling of the middle cerebral artery (MCA), in parallel with hypertension, compared with lean controls. This study tested the hypothesis that hypertension is an essential determinant of cerebral vascular remodeling and increased stroke damage in OZRs. Blood pressure was measured by telemetery in lean and obese rats with and without hydrochlorthiazide (HCT; 2 mg·kg -1·day-1) from 8 to 15 wk of age. A separate group of rats was also chronically fed a low-sodium (LS) diet. Vessel structure was assessed in isolated, pressurized MCAs. Cerebral ischemia was induced for 60 min using an intralumenal suture technique, followed by 24 h of reperfusion. HCT treatment effectively prevented the increase in blood pressure in obese rats; however, the LS diet did not lower pressure. Importantly, infarct size was normalized by HCT after ischemia-reperfusion injury. Additionally, HCT improved the changes in MCA structure observed in untreated OZRs. There were no benefits of the LS diet on stroke injury or vessel structure. These results indicate that increased pressure is essential for driving the changes in infarct size in OZRs.

AB - Obesity is a risk factor for stroke, but the determinants of increased stroke risk in obesity are unknown. We have previously reported that obese Zucker rats (OZRs) have a worse stroke outcome and display evidence of remodeling of the middle cerebral artery (MCA), in parallel with hypertension, compared with lean controls. This study tested the hypothesis that hypertension is an essential determinant of cerebral vascular remodeling and increased stroke damage in OZRs. Blood pressure was measured by telemetery in lean and obese rats with and without hydrochlorthiazide (HCT; 2 mg·kg -1·day-1) from 8 to 15 wk of age. A separate group of rats was also chronically fed a low-sodium (LS) diet. Vessel structure was assessed in isolated, pressurized MCAs. Cerebral ischemia was induced for 60 min using an intralumenal suture technique, followed by 24 h of reperfusion. HCT treatment effectively prevented the increase in blood pressure in obese rats; however, the LS diet did not lower pressure. Importantly, infarct size was normalized by HCT after ischemia-reperfusion injury. Additionally, HCT improved the changes in MCA structure observed in untreated OZRs. There were no benefits of the LS diet on stroke injury or vessel structure. These results indicate that increased pressure is essential for driving the changes in infarct size in OZRs.

KW - Hydrochlorothiazide

KW - Hypertension

KW - Vascular remodeling

UR - http://www.scopus.com/inward/record.url?scp=77953783839&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953783839&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.01111.2009

DO - 10.1152/ajpheart.01111.2009

M3 - Article

VL - 299

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 1

ER -