Iron deficiency suppresses ileal nitric oxide synthase activity.

M. I. Goldblatt, S. H. Choi, D. A. Swartz-Basile, A. Nakeeb, S. K. Sarna, H. A. Pitt

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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, Nomega-nitro-L-arginine (L-NNA), an NOS inhibitor, and VIP(10-28), 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/cm(2) vs. 1.5 +/- 0.3 N/cm(2), 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). VIP(10-28) 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 VIP(10-28) 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.

Original languageEnglish (US)
JournalJournal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
Volume5
Issue number4
StatePublished - Jul 2001
Externally publishedYes

Fingerprint

Nitric Oxide Synthase
Iron
Acetylcholine
Electric Stimulation
Nitric Oxide
Sciuridae
Gastrointestinal Motility
Muscle Relaxation
Iron-Deficiency Anemias
Vasoactive Intestinal Peptide
Muscle Contraction
Heme
Ileum
Edetic Acid
Oxides
Smooth Muscle
Neurotransmitter Agents
Arginine
Down-Regulation
Diet

ASJC Scopus subject areas

  • Surgery

Cite this

Iron deficiency suppresses ileal nitric oxide synthase activity. / Goldblatt, M. I.; Choi, S. H.; Swartz-Basile, D. A.; Nakeeb, A.; Sarna, S. K.; Pitt, H. A.

In: Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, Vol. 5, No. 4, 07.2001.

Research output: Contribution to journalArticle

Goldblatt, M. I. ; Choi, S. H. ; Swartz-Basile, D. A. ; Nakeeb, A. ; Sarna, S. K. ; Pitt, H. A. / Iron deficiency suppresses ileal nitric oxide synthase activity. In: Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2001 ; Vol. 5, No. 4.
@article{3168160b86364f7985848dac43fb572f,
title = "Iron deficiency suppresses ileal nitric oxide synthase activity.",
abstract = "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, Nomega-nitro-L-arginine (L-NNA), an NOS inhibitor, and VIP(10-28), 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/cm(2) vs. 1.5 +/- 0.3 N/cm(2), 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). VIP(10-28) 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 VIP(10-28) 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.",
author = "Goldblatt, {M. I.} and Choi, {S. H.} and Swartz-Basile, {D. A.} and A. Nakeeb and Sarna, {S. K.} and Pitt, {H. A.}",
year = "2001",
month = "7",
language = "English (US)",
volume = "5",
journal = "Journal of Gastrointestinal Surgery",
issn = "1091-255X",
publisher = "Springer New York",
number = "4",

}

TY - JOUR

T1 - Iron deficiency suppresses ileal nitric oxide synthase activity.

AU - Goldblatt, M. I.

AU - Choi, S. H.

AU - Swartz-Basile, D. A.

AU - Nakeeb, A.

AU - Sarna, S. K.

AU - Pitt, H. A.

PY - 2001/7

Y1 - 2001/7

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, Nomega-nitro-L-arginine (L-NNA), an NOS inhibitor, and VIP(10-28), 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/cm(2) vs. 1.5 +/- 0.3 N/cm(2), 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). VIP(10-28) 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 VIP(10-28) 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, Nomega-nitro-L-arginine (L-NNA), an NOS inhibitor, and VIP(10-28), 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/cm(2) vs. 1.5 +/- 0.3 N/cm(2), 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). VIP(10-28) 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 VIP(10-28) 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.

UR - http://www.scopus.com/inward/record.url?scp=19044379422&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=19044379422&partnerID=8YFLogxK

M3 - Article

VL - 5

JO - Journal of Gastrointestinal Surgery

JF - Journal of Gastrointestinal Surgery

SN - 1091-255X

IS - 4

ER -