Accession Number:

ADA628168

Title:

Hemorrhagic Shock-Induced Vascular Hyporeactivity in the Rat: Relationship to Gene Expression of Nitric Oxide Synthase, Endothelin-1, and Select Cytokines in Corresponding Organs

Descriptive Note:

Journal article

Corporate Author:

ARMY INST OF SURGICAL RESEARCH FORT SAM HOUSTON TX

Personal Author(s):

Report Date:

2005-01-01

Pagination or Media Count:

10.0

Abstract:

Background. Our previous work observed that vascular hyporeactivity to norepinephrine NE developed after hemorrhage and the response was not the same in the 4 arteries examined. To evaluate possible mechanisms involved, the present study investigated the gene expression of iNOS, eNOS, IL-1 Beta , IL-6, TNF-alpha , and endothelin-1 in the corresponding organs, and the roles of nitric oxide NO and endothelin ET. Materials and methods. LAnesthetized rats n 7time pointgroup were hemorrhaged to a mean arterial pressure of 50 mmHg for 60 min. The vascular reactivity of the superior mesenteric SMA, celiac CA, left renal LRA, and left femoral arteries LFA to NE was measured at baseline, at the end of the hypotensive period E, and at 1, 2, an d 4 h later in the three groups hemorrhage, hemorrhage NG-nitro-L-arginine methyl ester L -NAME, an NO synthase inhibitor, or hemorrhage PD142893, an ET receptor antagonist. Gene expression inileum, left kidney, liver, and skeletal muscle was determined by quantitative RT-PCR at these times. Results. Vascular reactivity of SMA, CA, LRA, and LFA to NE decreased as much as 98 over 4 h compared with baseline. This loss of responsiveness in CA and LFA was more severe than in SMA and LRA. Gene expression of iNOS, eNOS, IL-1 beta, IL-6, TNF-alpha, and endothelin-1 in the corresponding organs of select vasculatures increased markedly over baseline levels and the fold increase in mRNA levels of these enzymes and mediators in liver and skeletal muscle was higher than in ileum and left kidney. For example, at 4 h, iNOS expression was over 16-fold higher than baseline in liver and skeletal muscle, but 5- and 7-fold higher in ileum and kidney, respectively. L -NAME or PD142893 partially attenuated the decreased vascular reactivity induced by hemorrhagic shock and attenuated the changes in gene expression observed.

Subject Categories:

  • Biochemistry
  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE