Effect of leukotriene receptor antagonists on vascular permeability during endotoxic shock
- Medical Univ. of South Carolina, Charleston (USA)
Evidence has accumulated that sulfidopeptide leukotrienes are significant pathogenic mediators of certain hematologic and hemodynamic sequelae of endotoxic shock. In the present study, the effects of a selective LTD4/E4 receptor antagonist, LY171883 (LY), or a selective LTD4 receptor antagonist, SKF-104353 (SKF), were assessed on splanchnic and pulmonary localization of 99mTechnetium-labeled human serum albumin (99mTc-HSA) in acute endotoxic shock in the rat. Dynamic gamma camera imaging of heart (H), midabdominal (GI), and lung regions of interest generated time activity curves for baseline and at 5-35 min after Salmonella enteritidis endotoxin (10 mg/kg, i.v.). Slopes of GI/H and lung/H activity (permeability index, GI/H or lung/H X 10(-3)/min) provided indices of intestinal and lung localization. Rats received LY (30 mg/kg, i.v.), LY vehicle (LY Veh), SKF (10 mg/kg), or SKF vehicle (SK Veh) 10 min prior to endotoxin or endotoxin vehicle. In rats receiving the LY Veh and endotoxin (n = 8) or SKF Veh and endotoxin (n = 12), the splanchnic permeability indices to 99mTc-HSA were increased 11.2-fold and 5.1-fold, respectively (P less than 0.05) compared to vehicle control groups not given endotoxin (n = 5). Pulmonary permeability index for 99mTc-HSA was increased (P less than 0.05) to a lesser extent (3.2-fold) by endotoxin compared to vehicle controls. Pretreatment with SKF reduced the mesenteric permeability index to control levels (P less than 0.05) during the 5-35 min time interval post-endotoxin. LY reduced the mesenteric permeability index by 70%. Pulmonary relative permeability to 99mTc-HSA was not affected by LY pretreatment. Both splanchnic and lung relative permeability to the isotope was transient; at 135-225 min post-endotoxin, splanchnic localization of 99mTc-HSA (n = 4) was not significantly different from vehicle controls in these vascular beds.
- OSTI ID:
- 6247950
- Journal Information:
- Circulatory Shock; (USA), Vol. 32:3; ISSN 0092-6213
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
BACTERIAL DISEASES
PATHOGENESIS
BLOOD VESSELS
PERMEABILITY
PEPTIDES
BIOLOGICAL FUNCTIONS
ABDOMEN
ALBUMINS
GAMMA CAMERAS
HEART
IMAGE PROCESSING
ISOMERIC NUCLEI
LUNGS
PROSTAGLANDINS
RATS
RECEPTORS
SALMONELLA
TECHNETIUM 99
ANIMALS
BACTERIA
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
BODY AREAS
CAMERAS
CARDIOVASCULAR SYSTEM
DISEASES
FUNCTIONS
HOURS LIVING RADIOISOTOPES
INFECTIOUS DISEASES
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MAMMALS
MEMBRANE PROTEINS
MICROORGANISMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PROCESSING
PROTEINS
RADIOISOTOPES
RESPIRATORY SYSTEM
RODENTS
TECHNETIUM ISOTOPES
VERTEBRATES
YEARS LIVING RADIOISOTOPES
550601* - Medicine- Unsealed Radionuclides in Diagnostics
550901 - Pathology- Tracer Techniques