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Effect of NG-nitro-L-arginine-methyl-ester on cardiopulmonary function and biosynthesis of cyclooxygenase products during porcine endotoxemia.
Crit Care Med. 1997 Jun; 25(6):1051-8.CC

Abstract

OBJECTIVE

To determine if inhibition of nitric oxide synthase with NG-nitro-L-arginine-methyl-ester (L-NAME) potentiates endotoxin-induced cardiopulmonary dysfunction and release of cyclooxygenase products in a porcine model of endotoxemia.

DESIGN

Prospective, multiple group, controlled experimental study.

SETTING

Physiologic research laboratory at a veterinary medicine college.

SUBJECTS

Fifty-seven domestic pigs (mean 28.7 +/- 0.8 [SEM] kg).

INTERVENTIONS

Pentobarbital-anesthetized pigs were intubated and mechanically ventilated to normocapnia with room air. A ther-modilution cardiac output catheter was advanced into the pulmonary artery. Additional catheters were inserted into the jugular and femoral veins and femoral artery. The pigs received the following infusions: saline (control, n = 5); L-NAME (0.1, 0.5, 2.2, or 5.5 mg/ kg/hr, from -0.5 to 2 hrs, n = 16); Escherichia coli endotoxin (5 micrograms/ kg from 0 to 1 hr followed by 2 micrograms/kg from 1 to 2 hrs, i.v., n = 14); L-NAME plus endotoxin (n = 9); indomethacin plus endotoxin (n = 6); or L-NAME indomethacin plus endotoxin (n = 7).

MEASUREMENTS AND MAIN RESULTS

L-NAME significantly (p < .05) worsened endotoxin-induced hypoxemia and enhanced the increases in pulmonary vascular resistance index and systemic vascular resistance index at 30 to 60 mins. Endotoxin increased (p < .05) plasma concentrations of thromboxane B2 by seven- to eight-fold at 30 to 120 mins and 6-keto-prostaglandin F1 alpha by 16- to 24-fold at 60 to 120 mins. L-NAME enhanced (additive effect) endotoxin-induced increases in plasma concentrations of thromboxane B2 (60 mins) and significantly (p < .05) potentiated the increases in 6-keto-prostaglandin F1 alpha (120 mins). At 120 mins of endotoxemia, indomethacin (cyclooxygenase inhibitor) plus L-NAME markedly increased (p < .05, synergistic effect) systemic vascular resistance index compared with endotoxemic pigs pretreated with either L-NAME or indomethacin.

CONCLUSIONS

During endotoxemia, inhibition of nitric oxide synthase with L-NAME may be deleterious to cardiopulmonary function, as evidence by potentiation of endotoxin-induced systemic and pulmonary vasoconstriction, impairment of gas exchange, and enhanced biosynthesis of cyclooxygenase products. Moreover, during endotoxemia, the concomitant inhibition of two important vasodilators (i.e., nitric oxide and prostacyclin) is associated with a potentiated (p < .05) increase in systemic vascular resistance index.

Authors+Show Affiliations

Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9201060

Citation

Hellyer, P W., et al. "Effect of NG-nitro-L-arginine-methyl-ester On Cardiopulmonary Function and Biosynthesis of Cyclooxygenase Products During Porcine Endotoxemia." Critical Care Medicine, vol. 25, no. 6, 1997, pp. 1051-8.
Hellyer PW, Johnson LW, Olson NC. Effect of NG-nitro-L-arginine-methyl-ester on cardiopulmonary function and biosynthesis of cyclooxygenase products during porcine endotoxemia. Crit Care Med. 1997;25(6):1051-8.
Hellyer, P. W., Johnson, L. W., & Olson, N. C. (1997). Effect of NG-nitro-L-arginine-methyl-ester on cardiopulmonary function and biosynthesis of cyclooxygenase products during porcine endotoxemia. Critical Care Medicine, 25(6), 1051-8.
Hellyer PW, Johnson LW, Olson NC. Effect of NG-nitro-L-arginine-methyl-ester On Cardiopulmonary Function and Biosynthesis of Cyclooxygenase Products During Porcine Endotoxemia. Crit Care Med. 1997;25(6):1051-8. PubMed PMID: 9201060.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of NG-nitro-L-arginine-methyl-ester on cardiopulmonary function and biosynthesis of cyclooxygenase products during porcine endotoxemia. AU - Hellyer,P W, AU - Johnson,L W, AU - Olson,N C, PY - 1997/6/1/pubmed PY - 1997/6/1/medline PY - 1997/6/1/entrez SP - 1051 EP - 8 JF - Critical care medicine JO - Crit Care Med VL - 25 IS - 6 N2 - OBJECTIVE: To determine if inhibition of nitric oxide synthase with NG-nitro-L-arginine-methyl-ester (L-NAME) potentiates endotoxin-induced cardiopulmonary dysfunction and release of cyclooxygenase products in a porcine model of endotoxemia. DESIGN: Prospective, multiple group, controlled experimental study. SETTING: Physiologic research laboratory at a veterinary medicine college. SUBJECTS: Fifty-seven domestic pigs (mean 28.7 +/- 0.8 [SEM] kg). INTERVENTIONS: Pentobarbital-anesthetized pigs were intubated and mechanically ventilated to normocapnia with room air. A ther-modilution cardiac output catheter was advanced into the pulmonary artery. Additional catheters were inserted into the jugular and femoral veins and femoral artery. The pigs received the following infusions: saline (control, n = 5); L-NAME (0.1, 0.5, 2.2, or 5.5 mg/ kg/hr, from -0.5 to 2 hrs, n = 16); Escherichia coli endotoxin (5 micrograms/ kg from 0 to 1 hr followed by 2 micrograms/kg from 1 to 2 hrs, i.v., n = 14); L-NAME plus endotoxin (n = 9); indomethacin plus endotoxin (n = 6); or L-NAME indomethacin plus endotoxin (n = 7). MEASUREMENTS AND MAIN RESULTS: L-NAME significantly (p < .05) worsened endotoxin-induced hypoxemia and enhanced the increases in pulmonary vascular resistance index and systemic vascular resistance index at 30 to 60 mins. Endotoxin increased (p < .05) plasma concentrations of thromboxane B2 by seven- to eight-fold at 30 to 120 mins and 6-keto-prostaglandin F1 alpha by 16- to 24-fold at 60 to 120 mins. L-NAME enhanced (additive effect) endotoxin-induced increases in plasma concentrations of thromboxane B2 (60 mins) and significantly (p < .05) potentiated the increases in 6-keto-prostaglandin F1 alpha (120 mins). At 120 mins of endotoxemia, indomethacin (cyclooxygenase inhibitor) plus L-NAME markedly increased (p < .05, synergistic effect) systemic vascular resistance index compared with endotoxemic pigs pretreated with either L-NAME or indomethacin. CONCLUSIONS: During endotoxemia, inhibition of nitric oxide synthase with L-NAME may be deleterious to cardiopulmonary function, as evidence by potentiation of endotoxin-induced systemic and pulmonary vasoconstriction, impairment of gas exchange, and enhanced biosynthesis of cyclooxygenase products. Moreover, during endotoxemia, the concomitant inhibition of two important vasodilators (i.e., nitric oxide and prostacyclin) is associated with a potentiated (p < .05) increase in systemic vascular resistance index. SN - 0090-3493 UR - https://www.unboundmedicine.com/medline/citation/9201060/Effect_of_NG_nitro_L_arginine_methyl_ester_on_cardiopulmonary_function_and_biosynthesis_of_cyclooxygenase_products_during_porcine_endotoxemia_ L2 - https://dx.doi.org/10.1097/00003246-199706000-00024 DB - PRIME DP - Unbound Medicine ER -