PMID- 8335573
OWN - NLM
STAT- MEDLINE
DCOM- 19930826
LR  - 20220310
IS  - 8750-7587 (Print)
IS  - 0161-7567 (Linking)
VI  - 74
IP  - 5
DP  - 1993 May
TI  - Tumor necrosis factor-alpha inhibits endothelium-dependent relaxation.
PG  - 2394-403
AB  - Tumor necrosis factor-alpha (TNF-alpha) stimulates nitric oxide (NO) in vascular 
      endothelium by induction of the enzyme NO synthase II (NOS II). We examined the 
      effects of TNF-alpha on 1) endothelium-dependent (EDR) and 
      endothelium-independent (EIR) relaxation and 2) contraction of bovine intralobar 
      pulmonary arteries (BPA) and veins (BPV) in vitro. Acetylcholine (ACh), 
      bradykinin (BK), histamine, and A23187 produced EDR of BPA contracted with a 50% 
      effective concentration of U-46619 (15 nM), because relaxation was abolished by 
      endothelium-rubbing and attenuated by L-NG-mono-methylarginine (L-NMMA; 300 
      microM). TNF-alpha (0.00417, 0.0417, 0.417, and 1.25 micrograms/ml) incubated 
      with BPA for 60 min inhibited EDR of the BPA to ACh, BK, and histamine. The 
      effects of TNF required 30 min for onset. Recovery of EDR occurred 3-4 h after 
      washout of TNF-alpha. Pentoxifylline (1 microM) did not affect ACh-induced EDR 
      but selectively reversed TNF-alpha-mediated inhibition of ACh-induced EDR. 
      TNF-alpha-mediated inhibition of EDR was not reversible by L-NMMA, an inhibitor 
      of NOS I and NOS II, the cyclooxygenase inhibitor ibuprofen, or CV-3908 (1 
      microM), a platelet-activating factor antagonist. The inhibitory effect of 
      TNF-alpha on EDR was not mediated by nonspecific sensitization of the endothelium 
      to human protein because recombinant human granulocyte colony-stimulating factor 
      (10, 50, and 500 x 10(3) U/ml) did not affect EDR of BPA. The effect of TNF-alpha 
      was specific for release of NO from the endothelium of BPA because TNF-alpha did 
      not affect 1) EDR of BPV to ACh, BK, or ATP; 2) EIR of BPA or BPV to 
      nitroprusside; and 3) contraction of either BPA or BPV to KCl, U-46619, 
      histamine, norepinephrine, or serotonin. Thus TNF-alpha appears to selectively 
      inhibit receptor-mediated EDR and NO release in BPA. TNF-alpha-mediated 
      inhibition of EDR differs from that of L-arginine-based inhibitors and may 
      represent an endogenous physiological mechanism of regulation of NO in the 
      endothelium.
FAU - Greenberg, S
AU  - Greenberg S
AD  - Department of Medicine, Louisiana State University Medical Center, New Orleans 
      70112.
FAU - Xie, J
AU  - Xie J
FAU - Wang, Y
AU  - Wang Y
FAU - Cai, B
AU  - Cai B
FAU - Kolls, J
AU  - Kolls J
FAU - Nelson, S
AU  - Nelson S
FAU - Hyman, A
AU  - Hyman A
FAU - Summer, W R
AU  - Summer WR
FAU - Lippton, H
AU  - Lippton H
LA  - eng
GR  - HL-11802/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Appl Physiol (1985)
JT  - Journal of applied physiology (Bethesda, Md. : 1985)
JID - 8502536
RN  - 0 (Prostaglandin Endoperoxides, Synthetic)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vasoconstrictor Agents)
RN  - 27JT06E6GR (omega-N-Methylarginine)
RN  - 660YQ98I10 (Potassium Chloride)
RN  - 76898-47-0 (15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid)
RN  - 820484N8I3 (Histamine)
RN  - 94ZLA3W45F (Arginine)
RN  - N9YNS0M02X (Acetylcholine)
RN  - SD6QCT3TSU (Pentoxifylline)
RN  - WK2XYI10QM (Ibuprofen)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Arginine/analogs & derivatives/pharmacology
MH  - Cattle
MH  - Endothelium, Vascular/drug effects/*physiology
MH  - Histamine/pharmacology
MH  - Ibuprofen/pharmacology
MH  - In Vitro Techniques
MH  - Muscle Contraction/drug effects
MH  - Muscle Relaxation/drug effects
MH  - Muscle, Smooth, Vascular/*drug effects
MH  - Norepinephrine/pharmacology
MH  - Pentoxifylline/pharmacology
MH  - Potassium Chloride/pharmacology
MH  - Prostaglandin Endoperoxides, Synthetic/pharmacology
MH  - Pulmonary Artery/drug effects
MH  - Pulmonary Veins/drug effects
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Vasoconstrictor Agents/pharmacology
MH  - omega-N-Methylarginine
EDAT- 1993/05/01 00:00
MHDA- 1993/05/01 00:01
CRDT- 1993/05/01 00:00
PHST- 1993/05/01 00:00 [pubmed]
PHST- 1993/05/01 00:01 [medline]
PHST- 1993/05/01 00:00 [entrez]
AID - 10.1152/jappl.1993.74.5.2394 [doi]
PST - ppublish
SO  - J Appl Physiol (1985). 1993 May;74(5):2394-403. doi: 
      10.1152/jappl.1993.74.5.2394.