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Prolonged Exposure of Rats to Bacterial Lipopolysaccharide Accelerates Mortality and blunts Hemodynamic and Renal Effects of Endotoxemia in Sex‐Specific Fashions
Author(s) -
Wedn Abdalla M,
ElGowilly Sahar M,
ElMas Mahmoud M
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.513.4
Subject(s) - endocrinology , medicine , lipopolysaccharide , creatinine , renal function , kidney , hemodynamics , bolus (digestion) , blood pressure , sepsis , mean arterial pressure , heart rate
Although the biological effects of endotoxemia have been the subject of extensive investigation, widely different exposure times to endotoxic insults have been employed in reported studies. The current study is an attempt to systematically evaluate the effect of the duration of the endotoxic offence and rat sex on survivability and cardiovascular and renal functions. Rats were injected with i.p. lipopolysaccharide (LPS) once (5 mg/kg) or twice (5 mg/kg/day for 2 consecutive days). Systolic blood pressure (SBP), serum urea and creatinine, renal iNOS expression and responsiveness of isolated perfused kidneys to cumulative bolus injections of acetylcholine (ACh, 0.01–7.29 nmol) or N‐ethylcarboxamidoadenosine (NECA, adenosine analogue, 1.6–100 nmol) were evaluated after 6 hr of the first LPS injection or 1, 2, or 6 days later. Compared with control rats, a single 6‐hr challenge with LPS reduced SBP and renal vasodilatory responses to NECA, but not ACh, and elevated serum urea and creatinine and renal iNOS expression. These effects were sex independent as they were demonstrated in rat sexes. Except for LPS hypotension in male rats, these parameters were restored to near‐control levels 1 day after the septic insult. After 2‐day LPS (i) serum markers of renal function and renal iNOS expression remained unchanged in both rat sexes, (ii) ACh and NECA renal vasodilations were increased in male, but not female, preparations, and (ii) falls in SBP were observed irrespective of rat sex. All hemodynamic or renal parameters were normalized when measured 6 days after endotoxic insult in both male and female rats. Alternatively, the rat mortality was progressively increased over the 6‐day of the study, with this effect being more apparent in male compared with female rats. Our data suggest that the duration of LPS exposure, rat sex, and specific biologic activity are important determinant of the magnitude and direction of the biological effects of endotoxemia. Support or Funding Information Supported by the Science and Technology Development Fund, Egypt (STDF Grant No. 14895) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .