Effects of lipopolysaccharide-induced septic shock on rat isolated kidney, possible role of nitric oxide and protein kinase C pathways

Document Type: Original Article

Authors

1 Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Emam zaman Hospital, Mashhad, Iran

Abstract

Objective(s): Pathophysiology of sepsis-associated renal failure (one of the most common cause of death in intensive care units) had not been fully determined. The effect of nitric oxide and protein kinase C (PKC) pathways in isolated kidney of Lipopolysaccharide-treated (LPS) rats were investigated in this study.
Materials and Methods: Vascular responsiveness to phenylephrine and acetylcholine in the presence and absence of a potent PKC inhibitor (chelerythrine) and nonspecific NO inhibitor (L-NAME) as well as responses to acetylcholine and sodium nitroprusside (SNP) were examined.
Results: LPS (10 mg/kg, IP) treatment resulted in a lower systemic pressure and reduction of responses to vasoconstrictor and vasodilator agents (PConclusion: Present study highlighted that five hours of intraperitoneal endotoxin injection is adequate to reduce renal basal perfusion pressure. These results also suggest that PKC inhibition may have a beneficial role in vascular hyporesponsiveness induced by LPS. Although our study partly elaborated on the effects of LPS on isolated renal vascular responses to vasoactive agents, further studies are required to explain how LPS exerts its renal vascular effects.

Keywords

Main Subjects


1. Parrillo JE. Pathogenetic mechanisms of septic shock. New England Journal of Medicine 1993; 328:1471-1477.
2. Opal SM. Endotoxins and other sepsis triggers. Contrib Nephrol 2010; 167:14-24.
3. Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med 2004; 351:159-169.
4. Doi K. Role of kidney injury in sepsis. J Intensive Care 2016; 4:17-23.
5. Kellum JA, Lameire N. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care 2013; 17:204-219.
6. Langenberg C, Wan L, Egi M, May CN, Bellomo R. Renal blood flow in experimental septic acute renal failure. Kidney Int 2006; 69:1996-2002.
7. Gomez H, Ince C, De Backer D, Pickkers P, Payen D, Hotchkiss J, et al. A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury. Shock 2014; 41:3-11.
8. Bougle A, Duranteau J. Pathophysiology of sepsis-induced acute kidney injury: the role of global renal blood flow and renal vascular resistance. Contrib Nephrol 2011; 174:89-97.
9. Schwartz D, Mendonca M, Schwartz I, Xia Y, Satriano J, Wilson CB, et al. Inhibition of constitutive nitric oxide synthase (NOS) by nitric oxide generated by inducible NOS after lipopolysaccharide administration provokes renal dysfunction in rats. J Clin Invest 1997; 100:439-448.
10. Piepot HA, Boer C, Groeneveld AB, Van Lambalgen AA, Sipkema P. Lipopolysaccharide impairs endothelial nitric oxide synthesis in rat renal arteries. Kidney Int 2000; 57:2502-2510.
11.Titheradge MA. Nitric oxide in septic shock. Biochim Biophys Acta 1999; 1411:437-455.
12. Hattori Y, Hattori S, Kasai K. Lipopolysaccharide activates Akt in vascular smooth muscle cells resulting in induction of inducible nitric oxide synthase through nuclear factor-kappa B activation. Eur J Pharmacol 2003; 481:153-158.
13. Karimi G, Fatehi Z, Gholamnejad Z. The role of nitric oxide and protein kinase C in lipopolysaccharidemediated vascular hyporeactivity. J Pharm Pharm Sci 2006; 9:119-123.
14. Fatehi M, Anvari K, Fatehi-Hassanabad Z. The beneficial effects of protein tyrosine kinase inhibition on the circulatory failure induced by endotoxin in the rat. Shock 2002; 18:450-455.
15. Carcillo JA, Litten RZ, Suba EA, Roth BL. Alterations in rat aortic alpha 1-adrenoceptors and alpha 1-adrenergic stimulated phosphoinositide hydrolysis in intraperitoneal sepsis. Circ Shock 1988; 26:331-339.
16. Cavaillon JM, Adib-Conquy M, Fitting C, Adrie C, Payen D. Cytokine cascade in sepsis. Scand J Infect Dis 2003; 35:535-544.
17. Hartemink KJ, Groeneveld AB. Vasopressors and inotropes in the treatment of human septic shock: effect on innate immunity? Inflammation 2012; 35:206-213.
18. Wallis G, Brackett D, Lerner M, Kotake Y, Bolli R, McCay PB. In vivo spin trapping of nitric oxide generated in the small intestine, liver, and kidney during the development of endotoxemia: a time-course study. Shock 1996; 6:274-278.
19. Salter M, Knowles RG, Moncada S. Widespread tissue distribution, species distribution and changes in activity of Ca(2+)-dependent and Ca(2+)-independent nitric oxide synthases. FEBS Lett 1991; 291:145-149.
20. Kowalczyk A, Kleniewska P, Kolodziejczyk M, Skibska B, Goraca A. The role of endothelin-1 and endothelin receptor antagonists in inflammatory response and sepsis. Arch Immunol Ther Exp (Warsz) 2015; 63:41-52.
21. Fatehi-Hassanabad Z, Fatehi M, Shahidi MI. Endothelial dysfunction in aortic rings and mesenteric beds isolated from deoxycorticosterone acetate hypertensive rats: possible involvement of protein kinase C. Eur J Pharmacol 2004; 494:199-204.
22. Lang D, Terstesse M, Dohle F, Bangen P, Banas B, Pauels HG, et al. Protein kinase C (PKC) dependent induction of tissue factor (TF) by mesangial cells in response to inflammatory mediators and release during apoptosis. Br J Pharmacol 2002; 137:1116-1124.