Involvement of iNOS in postischemic heart dysfunction of stroke-prone spontaneously hypertensive rats

Kohji Abe, Miwa Tokumura, Tetsuji Ito, Takashi Murai, Akira Takashima, Nobuhiro Ibii

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Abstract

We investigated the possible contribution of inducible nitric oxide synthase (inos) to postischemic heart dysfunction and injuries in stroke-prone spontaneously hypertensive rats (shrsp). Shrsp, 13-14 wk of age, had significantly higher systolic blood pressure and greater heart weight than age-matched Wistar-Kyoto rats (WKY). Permanent occlusion of the left anterior descending coronary artery (LAD) caused significant and long-lasting increases in the activity and mRNA expression of myocardial iNOS in SHRSP compared with WKY. However, there was no significant difference in the LAD occlusion-induced expression of interleukin-1β mRNA between SHRSP and WKY. Hemodynamic deterioration and myocardial fibrosis were also observed in SHRSP at 4 wk after LAD occlusion. Continuous administration of 2-amino-5,6-dihydro-6-methyl-4H-1,2-thiazin (AMT) completely blocked the LAD occlusion-induced increase in the myocardial iNOS activity of SHRSP. Moreover, postischemic heart dysfunction and injuries were also significantly ameliorated by 2-amino-5,6-dihydro-6-methyl-4H-1,2-thiazin (AMT). These results suggest that the increased activity of myocardial iNOS plays a pivotal role in the development of postischemic cardiac dysfunction and injuries in SHRSP with the hypertensive and hypertrophic heart.

Original languageEnglish
Pages (from-to)H668-H673
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number2 49-2
Publication statusPublished - Feb 1 2001

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Keywords

  • 2-amino-5,6-dihydro-6-methyl-4H-1,2-thiazin
  • Cardiac hypertrophy
  • Left anterior descending coronary artery occlusion

ASJC Scopus subject areas

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

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