Coronary Microvascular Endothelial Stunning after Acute Pressure Overload in the Conscious Dog Is Caused by Oxidant Processes: The Role of Angiotensin II Type I Receptor and NAD(P)H Oxidase

Shintaro Kinugawa, Heiner Post, Pawel M. Kaminski, Xiaoping Zhang, Xiaobin Xu, Harer Huang, Fabio A. Recchia, Manuel Ochoa, Michael S. Wolin, Gabor Kaley, Thomas H. Hintze

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Background-Few studies have examined the effect of acute pressure overload on endothelial function in the coronary microcirculation. Methods and Results-In instrumented conscious dogs with heart rate held constant, veratrine caused a cholinergic nitric oxide (NO)-dependent increase in coronary blood flow by 23±3 mL/min (Bezold-Jarisch reflex). Ten minutes after release of constriction of the ascending aorta to increase left ventricular (LV) systolic pressure to 214±5 mm Hg for 30 minutes, the veratrine-induced increase in coronary blood flow (7±1 mL/min) was reduced by 66% and remained depressed for 2 hours (ie, endothelial stunning [ES]). Nitrite production from isolated coronary microvessels during ES was not different from normal. Ascorbic acid (AA), losartan, or apocynin prevented ES. Myocardial oxygen consumption (MV̇O2) of LV tissue was measured in vitro in response to bradykinin with preincubation of angiotensin II for 30 minutes. Bradykinin (10-4 mol/L)-induced reduction in MV̇O2 was reversed in a concentration-dependent manner by angiotensin II (38±1% versus 19±2% at 10-8 mol/L) and restored by coincubation of AA (37±2%), tempol (33±2%), losartan (34±2%), or apocynin (36±1%). Exogenous NO-induced reduction in MV̇O2 was not altered by angiotensin II. Angiotensin II increased lucigenin-detectable superoxide anion in LV tissue in a manner that was inhibited by bradykinin, AA, tempol, losartan, or apocynin. Conclusions-Endothelial stunning is caused by oxidant processes inhibited by ascorbate, and the activation of NAD(P)H oxidase by increased angiotensin II plays an important role in this process.

Original languageEnglish
Pages (from-to)2934-2940
Number of pages7
JournalCirculation
Volume108
Issue number23
DOIs
Publication statusPublished - Dec 9 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Coronary Microvascular Endothelial Stunning after Acute Pressure Overload in the Conscious Dog Is Caused by Oxidant Processes: The Role of Angiotensin II Type I Receptor and NAD(P)H Oxidase'. Together they form a unique fingerprint.

  • Cite this