Role of angiotensin II in neonatal sepsis.
Previous studies in adult animals have indicated that plasma angiotensin converting enzyme (ACE) activity is inhibited by endotoxin. Reduced ACE activity may decrease plasma angiotensin II (AII) levels, contributing to the refractory hypotension we have previously reported in neonatal septic shock. In this study, hemodynamic function, plasma renin activity (PRA), AII, prostacyclin (PGI2), and thromboxane B2 (TxB2) levels were measured in 17-20-day-old dogs before and 1, 2, and 3 hr after endotoxin administration (1 mg/kg, Escherichia coli lipopolysaccharide-B). PRA and AII levels rose significantly 60 min post-endotoxin, returning to baseline values by 180 min; PGI2 and thromboxane B2 levels rose post-endotoxin and remained elevated. Indomethacin or captopril was given by oral gavage 30-35 min before endotoxin. Captopril significantly blunted the rise in PRA and AII, while indomethacin blocked the rise in PGI2 and TxB2. Mean arterial blood pressure and cardiac output fell 60 min after endotoxin challenge without pharmacologic intervention and remained depressed. Our data suggest that renin and AII responses to endotoxin challenge remain intact in the neonatal subject. Maintenance of hemodynamics in indomethacin-pretreated dogs may be due to unopposed stimulation of the peripheral vasculature by AII. Thromboxane B2 in maintenance of vasomotor tone may be minimal in the young.
Department of Surgery, University of Texas Southwestern Medical Center, Dallas 75235-9031.
C W
CW
Dunn
J W
JW
Horton
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002216:Captopril / Q000494:pharmacology; D004285:Dogs; D011464:Epoprostenol / Q000097:blood; D004926:Escherichia coli; D006439:Hemodynamics; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides; D012083:Renin / Q000097:blood; D012772:Shock, Septic / Q000139:chemically induced / Q000503:physiopathology*; D013929:Thromboxane B2 / Q000097:blood
D008070:Lipopolysaccharides; C036757:lipopolysaccharide B; D000804:Angiotensin II; D013929:Thromboxane B2; D002216:Captopril; D011464:Epoprostenol; D012083:Renin; D007213:Indomethacin