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Department of Pediatrics, The Ohio State University and The Vascular Biology Laboratory, Children's Research Institute, Children's Hospital, Columbus, Ohio 43205
We studied mesenteric arterial
arcades from 3- and 35-day-old swine to determine the relationship
between perfusate flow rate and release of nitric oxide (NO) into
mesenteric effluent. Mesenteric arterial arcades were perfused under
controlled-flow conditions with a peristaltic pump using warm
oxygenated Krebs buffer. Basal rates of NO production were 43.6 ± 4.2 vs. 12.1 ± 2.5 nmol/min in 3- vs. 35-day-old mesentery during
perfusion at in vivo flow rates (9 vs. 20 ml/min, respectively). Rate
of NO production was directly related to flow rate over a wide range of
flows (5-40 ml/min) in 3- but not 35-day-old mesentery. Both age
groups demonstrated a brisk, albeit brief, increase in NO production in
response to infusion of NO-dependent vasodilator substance P
(10
8 M/min). Tyrosine kinase inhibitor herbimycin A and
L-arginine analog L-NMMA significantly
attenuated flow-induced increase in NO production, and phosphatase
inhibitor phenylarsine oxide increased magnitude of flow-induced
increase in NO production in 3-day-olds. Removal of extracellular
Ca2+ and depletion of intracellular Ca2+ stores
(Ca2+-free Krebs with EGTA plus thapsigargin) had no effect
on NO production in either group. Thus, basal rate of NO production is
greater in mesenteric arterial arcades from 3- than from 35-day old
swine, a direct relationship between flow rate and NO production rate is present in mesentery from 3- but not 35-day-olds, and
phosphorylation events are necessary for this interaction to occur.
phosphorylation; calcium; flow-induced dilation; newborn intestinal circulation
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