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.
Objective:To study the role of Na+, K+- ATPase enzyme in the vascular response of goat ruminal artery.Materials and Methods:Ruminal artery was obtained in chilled aerated modified Krebs-Henseleit solution (KHS) from a local slaughterhouse and transported in ice for further processing. The endothelium intact arterial ring was mounted in a thermostatically controlled (37 ± 0.5°C) organ bath containing 20 ml of modified KHS (pH 7.4) bubbled with oxygen (95%) and CO2 (5%) under 2g tension. An equilibration of 90 min was allowed before addition of drugs into the bath. The responses were recorded isometrically in an automatic organ bath connected to PowerLab data acquisition system. In order to examine intact functional endothelium, ACh (10 μM) was added on the 5-HT (1.0 μM) - induced sustained contractile response. Similarly, functional characterization of Na+, K+-ATPase activity was done by K+-induced relaxation (10 μM-10 mM) in the absence and presence of ouabain (0.1 μM/ 0.1 mM), digoxin (0.1 μM) and barium (30 μM).Results:ACh (10−5 M) did not produce any relaxing effect on 5-HT-induced sustained contractile response suggesting that vascular endothelium has no significant influence on the activation of sodium pump by extracellular K+ in ruminal artery. Low concentration of Ba2+ (30 μM) (IC50: 0.479 mM) inhibited K+-induced relaxation suggesting Kir (inward rectifier) channel in part had role in K+-induced vasodilatation in ruminal artery. Vasorelaxant effect of KCl (10 μM-10 mM) in K+-free medium is also blocked by ouabain (0.1 μM and 0.1 mM) (IC50:0.398 mM and IC35: 1.36 mM), but not by digoxin (0.1 μM) (IC50 0.234 mM) suggesting that ouabain sensitive Na+, K+-ATPase isoform is present in the ruminal artery.Conclusion:In the goat ruminal artery functional regulation of sodium pump is partly mediated by K+ channel and ouabain sensitive Na+, K+ ATPase.
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