Relationship between flow rate and NO production in postnatal mesenteric arteries.

Abstract

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 Ca(2+) and depletion of intracellular Ca(2+) stores (Ca(2+)-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.