Regional differences in the effects of septic shock on vascular reactivity in the rabbit.
Experiments were performed to investigate the vascular reactivity in both large and resistance artery preparations from an animal model of septic shock. New Zealand White rabbits were injected with a priming dose of Escherichia coli lipopolysaccharide (LPS), 15 micrograms/kg i.v., 18 hr before an i.v. dose of 200 to 2000 micrograms/kg under pentobarbital anesthesia. The second LPS challenge dropped mean blood pressure from 79 +/- 4 to 27 +/- 5 mm Hg in approximately 1 hr. At this time animals were sacrificed with the central ear arteries and kidneys being isolated for alignment in a Krebs-bicarbonate buffer perfusion apparatus to monitor perfusion pressure under constant flow conditions. Individual dose-response curves (DRCs) for norepinephrine (NE) and histamine were performed to assess contractile function. For examining vascular relaxant function, DRCs for methacholine (MC) and nitroprusside (NP) were conducted during a submaximal infusion of NE. The DRCs to NE and histamine were shifted to the right by 2- and 2.7-fold, respectively, in isolated ear artery preparations from LPS-treated vs. vehicle-treated animals. There was no difference in contractile function (using NE) in the two groups of perfused kidneys. The relaxation DRCs to MC were similar in the ear artery preparations from the two treatment groups whereas, in isolated kidneys, the relaxation to MC was significantly attenuated, by an average of 26 +/- 2% at each of six doses, in preparations from LPS-treated animals. The relaxation to NP was similar between the LPS- and vehicle-treated animals in the ear artery and kidney preparations.(ABSTRACT TRUNCATED AT 250 WORDS)
Li
T
T
Department of Pharmacology, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut.
Croce
K
K
Winquist
R J
RJ
D000818:Animals; D004347:Drug Interactions; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects; D012772:Shock, Septic / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D009599:Nitroprusside; D006632:Histamine; D009638:Norepinephrine; D011224:Prazosin