TY - JOUR
T1 - Iron Deficiency Suppresses Ileal Nitric Oxide Synthase Activity
AU - Goldblatt, Matthew I.
AU - Choi, Seong Ho
AU - Swartz-Basile, Deborah A.
AU - Nakeeb, Atilla
AU - Sarna, Sushil K.
AU - Pitt, Henry A.
N1 - Funding Information:
From the Department of Surgery, Medical College of Wisconsin, Milwaukee, Wis.; and the Department of Surgery (S.-H.C.), SungkyunkwanU niversity School of Medicine, Seoul, South Korea. Supported by grant ROI-DK44279-07 from the National Institutes of Health. Presented at the Forty-First Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 2 l-24,2000. Reprint requests: Henry A. Pitt, M.D., Medical College of Wisconsin, 9200 West Wisconsin Ave., Milwaukee, WI 53226. e-mail: hapitt@mcw.edu
PY - 2001
Y1 - 2001
N2 - 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 relaxation and contraction, respectively. Iron-containing heme is known to be a cofactor for nitric oxide synthase (NOS), the enzyme responsible for NO production. Therefore we tested the hypothesis that iron deficiency would downregulate ileal NOS activity without affecting the ileum's response to ACh. Twelve 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 weeks. Ileal circular muscle strips were harvested to measure responses to ACh and electrical field stimulation. Under nonadrenergic noncholinergic (NANC) conditions, Nω-nitro-L-arginine (L-NNA), an NOS inhibitor, and VIP10-28, a vasoactive intestinal peptide (VIP) inhibitor, were added prior to electrical field stimulation. NANC inhibitory responses are expressed as a percentage of optimal relaxation from EDTA. The excitatory response to ACh was similar in both groups (1.1 ± 0.3 N/cm2 vs. 1.5 ± 0.3 N/cm2, P = 0.45). The inhibitory response to electrical field stimulation under NANC conditions 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 <0.01). VIP10-28 led to greater relaxation in the Fe+ animals (45.8 ± 6.6%) than in the Fe- animals (23.4 ± 5.8%; P <0.05). Both L-NNA and VIP10-28 had no inhibitory response (0.02 ± 0.02%) in the Fe+ animals, whereas the Fe- animals had some residual inhibition (2.54 ± 1.04%; P <0.05). These data suggest that ileal NANC relaxation is due to NOS and that iron deficiency results in (1) decreased NANC relaxation, (2) a compensatory relaxation due to a non-NOS, non-VIP mechanism, and (3) a normal excitatory response. We conclude that iron deficiency suppresses ileal NOS activity.
AB - 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 relaxation and contraction, respectively. Iron-containing heme is known to be a cofactor for nitric oxide synthase (NOS), the enzyme responsible for NO production. Therefore we tested the hypothesis that iron deficiency would downregulate ileal NOS activity without affecting the ileum's response to ACh. Twelve 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 weeks. Ileal circular muscle strips were harvested to measure responses to ACh and electrical field stimulation. Under nonadrenergic noncholinergic (NANC) conditions, Nω-nitro-L-arginine (L-NNA), an NOS inhibitor, and VIP10-28, a vasoactive intestinal peptide (VIP) inhibitor, were added prior to electrical field stimulation. NANC inhibitory responses are expressed as a percentage of optimal relaxation from EDTA. The excitatory response to ACh was similar in both groups (1.1 ± 0.3 N/cm2 vs. 1.5 ± 0.3 N/cm2, P = 0.45). The inhibitory response to electrical field stimulation under NANC conditions 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 <0.01). VIP10-28 led to greater relaxation in the Fe+ animals (45.8 ± 6.6%) than in the Fe- animals (23.4 ± 5.8%; P <0.05). Both L-NNA and VIP10-28 had no inhibitory response (0.02 ± 0.02%) in the Fe+ animals, whereas the Fe- animals had some residual inhibition (2.54 ± 1.04%; P <0.05). These data suggest that ileal NANC relaxation is due to NOS and that iron deficiency results in (1) decreased NANC relaxation, (2) a compensatory relaxation due to a non-NOS, non-VIP mechanism, and (3) a normal excitatory response. We conclude that iron deficiency suppresses ileal NOS activity.
KW - Ileum
KW - Iron deficiency
KW - Motility
KW - Nitric oxide synthase
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U2 - 10.1016/S1091-255X(01)80068-8
DO - 10.1016/S1091-255X(01)80068-8
M3 - Article
C2 - 11985981
AN - SCOPUS:19044379422
VL - 5
SP - 393
EP - 400
JO - Journal of Gastrointestinal Surgery
JF - Journal of Gastrointestinal Surgery
SN - 1091-255X
IS - 4
ER -