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Atorvastatin restores the impaired vascular endothelium-dependent relaxations mediated by nitric oxide and endothelium-derived hyperpolarizing factors but not hypotension in sepsis.
J Cardiovasc Pharmacol 2009; 54(6):526-34JC

Abstract

Sepsis has been reported to impair endothelium-dependent vasodilations mediated by nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Although some studies demonstrate that statins can improve NO-mediated response in septic animals, little is known about its effect on the EDHF response. The present study examined the effects of atorvastatin pretreatment on sepsis-induced endothelial dysfunctions and hypotension in rats. Eighteen hours after the induction of sepsis by cecal ligation and puncture, thoracic aorta and second generation pulmonary arteries were isolated to examine acetylcholine-induced endothelium-dependent dilations mediated by NO and EDHF, respectively. The messenger RNA (mRNA) expression for endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) was done by real-time polymerase chain reaction. NO was measured as nitrate/nitrite release using Griess method. Mean arterial pressure was measured by the invasive method. Sepsis significantly decreased (26%) the relaxation response to acetylcholine in the rat aorta. It also markedly inhibited the eNOS mRNA expression and acetylcholine-stimulated NO release in this vessel. Pretreatment of the rats with atorvastatin (10 mg/kg, orally) 48, 24, and 2 hours before induction of sepsis preserved acetylcholine-induced relaxation, eNOS mRNA expression, acetylcholine-stimulated NO release, and attenuated increase in the inducible NO synthase mRNA expression and basal NO production in the aorta. The maximal EDHF response mediated by acetylcholine was 25.30% +/- 3.00% in the pulmonary artery. Sepsis abolished this response but atorvastatin restored it (22.55% +/- 2.50%). Atorvastatin, however, failed to prevent sepsis-induced hypotension. These results suggest that atorvastatin can restore impaired endothelium-dependent vasodilations mediated by NO and EDHF but not hypotension in sepsis.

Authors+Show Affiliations

Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, U.P, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19755915

Citation

Subramani, Jaganathan, et al. "Atorvastatin Restores the Impaired Vascular Endothelium-dependent Relaxations Mediated By Nitric Oxide and Endothelium-derived Hyperpolarizing Factors but Not Hypotension in Sepsis." Journal of Cardiovascular Pharmacology, vol. 54, no. 6, 2009, pp. 526-34.
Subramani J, Kathirvel K, Leo MD, et al. Atorvastatin restores the impaired vascular endothelium-dependent relaxations mediated by nitric oxide and endothelium-derived hyperpolarizing factors but not hypotension in sepsis. J Cardiovasc Pharmacol. 2009;54(6):526-34.
Subramani, J., Kathirvel, K., Leo, M. D., Kuntamallappanavar, G., Uttam Singh, T., & Mishra, S. K. (2009). Atorvastatin restores the impaired vascular endothelium-dependent relaxations mediated by nitric oxide and endothelium-derived hyperpolarizing factors but not hypotension in sepsis. Journal of Cardiovascular Pharmacology, 54(6), pp. 526-34. doi:10.1097/FJC.0b013e3181bfafd6.
Subramani J, et al. Atorvastatin Restores the Impaired Vascular Endothelium-dependent Relaxations Mediated By Nitric Oxide and Endothelium-derived Hyperpolarizing Factors but Not Hypotension in Sepsis. J Cardiovasc Pharmacol. 2009;54(6):526-34. PubMed PMID: 19755915.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Atorvastatin restores the impaired vascular endothelium-dependent relaxations mediated by nitric oxide and endothelium-derived hyperpolarizing factors but not hypotension in sepsis. AU - Subramani,Jaganathan, AU - Kathirvel,Kandaswamy, AU - Leo,Marie Dennis Marcus, AU - Kuntamallappanavar,Guruprasad, AU - Uttam Singh,Thakur, AU - Mishra,Santosh Kumar, PY - 2009/9/17/entrez PY - 2009/9/17/pubmed PY - 2010/4/27/medline SP - 526 EP - 34 JF - Journal of cardiovascular pharmacology JO - J. Cardiovasc. Pharmacol. VL - 54 IS - 6 N2 - Sepsis has been reported to impair endothelium-dependent vasodilations mediated by nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Although some studies demonstrate that statins can improve NO-mediated response in septic animals, little is known about its effect on the EDHF response. The present study examined the effects of atorvastatin pretreatment on sepsis-induced endothelial dysfunctions and hypotension in rats. Eighteen hours after the induction of sepsis by cecal ligation and puncture, thoracic aorta and second generation pulmonary arteries were isolated to examine acetylcholine-induced endothelium-dependent dilations mediated by NO and EDHF, respectively. The messenger RNA (mRNA) expression for endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) was done by real-time polymerase chain reaction. NO was measured as nitrate/nitrite release using Griess method. Mean arterial pressure was measured by the invasive method. Sepsis significantly decreased (26%) the relaxation response to acetylcholine in the rat aorta. It also markedly inhibited the eNOS mRNA expression and acetylcholine-stimulated NO release in this vessel. Pretreatment of the rats with atorvastatin (10 mg/kg, orally) 48, 24, and 2 hours before induction of sepsis preserved acetylcholine-induced relaxation, eNOS mRNA expression, acetylcholine-stimulated NO release, and attenuated increase in the inducible NO synthase mRNA expression and basal NO production in the aorta. The maximal EDHF response mediated by acetylcholine was 25.30% +/- 3.00% in the pulmonary artery. Sepsis abolished this response but atorvastatin restored it (22.55% +/- 2.50%). Atorvastatin, however, failed to prevent sepsis-induced hypotension. These results suggest that atorvastatin can restore impaired endothelium-dependent vasodilations mediated by NO and EDHF but not hypotension in sepsis. SN - 1533-4023 UR - https://www.unboundmedicine.com/medline/citation/19755915/Atorvastatin_restores_the_impaired_vascular_endothelium_dependent_relaxations_mediated_by_nitric_oxide_and_endothelium_derived_hyperpolarizing_factors_but_not_hypotension_in_sepsis_ L2 - http://Insights.ovid.com/pubmed?pmid=19755915 DB - PRIME DP - Unbound Medicine ER -