Iron deficiency suppresses ileal nitric oxide synthase activity

Intestinal motility disorders are more common in women of childbearing age who are prone to iron deficiency anemia. The neurotransmitters nitric oxide (NO) and acetylcholine (ACh) play a key role in ileal smooth muscle relaxa tion and contraction, respectively. Iron-containing heme is known to be a c ofactor for nitric oxide synthase (NOS), the enzyme responsible for NO prod uction. Therefore we tested the hypothesis that iron deficiency would downr egulate ileal NOS activity without affecting the ileum's response to ACh. T welve adult female prairie dogs were fed either an iron-supplemented (Fe+) (200 ppm) (n = 6) or an iron-deficient (Fe-) (8 ppm) (n = 6) diet for 8 wee ks. Ileal circular muscle strips were harvested to measure responses to ACh and electrical field stimulation. Under nonadrenergic noncholinergic (NANC ) conditions, Nw-nitro-L-arginine (L-NNA), an NOS inhibitor, and VIP10-28, a vasoactive intestinal peptide (VIP) inhibitor, were added prior to electr ical field stimulation. NANC inhibitory responses are expressed as a percen tage of optimal relaxation from EDM. The excitatory response to ACh was sim ilar in both groups (1.1 +/- 0.3 N/cm(2) vs. 1.5 +/- 0.3 N/cm(2), P = 0.45) . The inhibitory response to electrical field stimulation under NANC condit ions was greater in the Fe+ group (34.7 +/- 2.9%) compared to the Fe- group (23.9 +/- 3.2%; P <0.01). L-NNA eliminated the inhibitory response in the Fe+ group (0.02 +/- 0.02%) but not in the Fe- group (8.38 +/- 2.15%; P <0-0 1). VIP10-28 led to greater relaxation in the Fe+ animals (45.8 +/- 6.6%) t han in the Fe- animals (23.4 +/- 5.8%; P <0.05). Both L-NNA and VIP10-28 ha d no inhibitory response (0.02 0.02%) in the Fe+ animals, whereas the Fe- a nimals had some residual inhibition (2.54 +/- 1.04%; P <0.05). These data s uggest that ileal NANC relaxation is due to NOS and that iron deficiency re sults in (1) decreased NANC relaxation, (2) a compensatory relaxation due t o a non-NOS, non-VIP mechanism, and (3) a normal excitatory response. We co nclude that iron deficiency suppresses ileal NOS activity.