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.

Developmental expression of eNOS in postnatal swine mesenteric artery

“…Present data confirm these past observations and provide a mechanistic basis for the greater constitutive (1,19,23) and stimulated (24,30,31) production of NO within the newborn intestinal circulation, i.e., that expression of eNOS within the mesenteric artery increases after birth and remains elevated for at least the first 10 days of postnatal life. It is critical to note, however, that the present study is insufficient to allow Fig.…”

“…Generation of cGMP by in vitro mesenteric artery under basal or stimulated conditions is greater in rings from 3-than from 35-day-old subjects (23). Finally, the concentration of total nitrates (NO x ) is significantly greater within the effluent of buffer-perfused mesenteric arterial arcades from 3-than from 35-day-old piglets, and a direct relationship between the buffer flow rate, mesenteric arcade vascular resistance, and the concentration of NO x in the effluent is present only in younger subjects (30). This relationship is consistent with the observation that flow-mediated dilation, a process that can be NO-dependent (17), can be elicited in the intestinal circulation of 3-but not 35-day-old piglets (24).…”

“…newborn intestine; necrotizing enterocolitis THE ROLE OF NITRIC OXIDE (NO) in regulation of porcine postnatal intestinal circulation is age specific, being more substantial in younger than older subjects (20,23,30). Thus blockade of endogenous NO synthesis with an L-arginine analog increases intestinal vascular resistance 45 Ϯ 4% in 3-day-old piglets but only 8 Ϯ 2% in 35-day-old subjects, whereas application of NO-dependent agonists (e.g., acetylcholine) causes a greater relaxation of phenylephrine-precontracted mesenteric artery rings from 3-than from 35-day-old piglets (20).…”

Simultaneous in situ monitoring of intracellular Ca2+and NO in endothelium of coronary arteries

“…It is well known that for some agonists, such as acetylcholine (29) and bradykinin (BK) (36), a rise in intracellular Ca 2ϩ is necessary for NO production. However, recent studies indicated that shear stress (9,30), isometric contraction (10), tyrosine phosphatase inhibitors (9,28,30), IGF-I (34), estrogen (5), and insulin (25) activate eNOS in isolated vessel preparations or in cultured cells in the absence of a change in [Ca 2ϩ ] i . These Ca 2ϩ -insensitive responses are blocked by tyrosine kinase inhibitors.…”

Intestinal O2 Consumption in Necrotizing Enterocolitis: Role of Nitric Oxide

“…A tissue slice was added to each well and the plate incubated at 37°C; thereafter, a second buffer sample was taken, the tissue slices were removed, blotted, and weighed. The NO concentration of conditioned buffer samples was determined by means of a Sievers NO Analyzer (Sievers Instruments, Boulder, CO) as previously reported (19). Paired observations were made for each perturbation and the average taken, and final data expressed as nM NO/L/g tissue.…”