Essential role of nitric oxide in sepsis-induced impairment of endothelium-derived hyperpolarizing factor-mediated relaxation in rat pulmonary artery

Jaganathan Subramani, Marie Dennis Leo, Kandaswamy Kathirvel, Rathinam Arunadevi, Thakur Uttam Singh, Vellanki Ravi Prakash, Santosh Kumar Mishra

Research output: Contribution to journalArticle

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Abstract

Both endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) are important vasodilators in pulmonary circulation. Sepsis is known to impair endothelium-dependent dilation in the pulmonary vasculature, but the mechanisms are incompletely understood. We have examined the relative contribution of EDHF/NO to the attenuated endothelium-dependent relaxation of pulmonary artery in sepsis, and the role of inducible nitric oxide synthase (iNOS)-derived NO in this mechanism. Sepsis was induced in male adult Wistar rats by caecal ligation and puncture. At 18h after surgery, left and right branches of pulmonary arteries were isolated for tension recording, NO/cyclic guanosine monophosphate (cGMP) measurements, mRNA and protein expressions. Despite a marked decrease in the arterial endothelial nitric oxide synthase (eNOS) mRNA and phosphorylated-eNOS (p-eNOS) protein expressions in sepsis, endothelium-dependent relaxation to acetylcholine (ACh) mediated by NO, acetylcholine-stimulated NO release and tissue cGMP levels were moderately inhibited. Sepsis however abolished the NG-Nitro-l-arginine methyl ester (L-NAME)/indomethacin-resistant arterial relaxation (EDHF response) to acetylcholine in this vessel. In vitro treatment of the arterial rings from septic rats with 1400W, a selective inhibitor of iNOS restored the EDHF response, but had no effect on the acetylcholine-induced relaxation mediated by endothelial NO. The functional role of iNOS-derived NO in impairing EDHF-mediated relaxation was coincident with an increased basal NO production, iNOS mRNA and protein expressions in the rat pulmonary artery. In conclusion, the loss of the EDHF response may be primarily responsible for the endothelial dysfunction in sepsis, and its restoration by a selective iNOS inhibitor may improve pulmonary vasodilation.

Original languageEnglish (US)
Pages (from-to)84-91
Number of pages8
JournalEuropean Journal of Pharmacology
Volume630
Issue number1-3
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

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Pulmonary Artery
Endothelium
Sepsis
Nitric Oxide
Nitric Oxide Synthase Type II
Acetylcholine
Nitric Oxide Synthase Type III
Cyclic GMP
Messenger RNA
Lung
Proteins
Pulmonary Circulation
NG-Nitroarginine Methyl Ester
Vasodilator Agents
Punctures
Vasodilation
Indomethacin
Ligation
Wistar Rats
Dilatation

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Essential role of nitric oxide in sepsis-induced impairment of endothelium-derived hyperpolarizing factor-mediated relaxation in rat pulmonary artery. / Subramani, Jaganathan; Leo, Marie Dennis; Kathirvel, Kandaswamy; Arunadevi, Rathinam; Singh, Thakur Uttam; Prakash, Vellanki Ravi; Mishra, Santosh Kumar.

In: European Journal of Pharmacology, Vol. 630, No. 1-3, 01.03.2010, p. 84-91.

Research output: Contribution to journalArticle

Subramani, Jaganathan ; Leo, Marie Dennis ; Kathirvel, Kandaswamy ; Arunadevi, Rathinam ; Singh, Thakur Uttam ; Prakash, Vellanki Ravi ; Mishra, Santosh Kumar. / Essential role of nitric oxide in sepsis-induced impairment of endothelium-derived hyperpolarizing factor-mediated relaxation in rat pulmonary artery. In: European Journal of Pharmacology. 2010 ; Vol. 630, No. 1-3. pp. 84-91.
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AU - Singh, Thakur Uttam

AU - Prakash, Vellanki Ravi

AU - Mishra, Santosh Kumar

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