title: Effect of nitric oxide synthase inhibition and saline administration on blood pressure and renal sodium handling during experimental sepsis in rats.
abstract: Much effort has been made in recent years to clarify metabolic and renal function changes in sepsis. A number of studies performed in different models of sepsis have been described. One such model that is frequently used is cecal ligation and puncture (CLP) in rats. This model resembles human sepsis in several important aspects, such as an early phase of hyperdynamic, hypermetabolic sepsis followed by a late hypodynamic, hypometabolic phase. The present study evaluated the blood pressure (n = 5) and renal function changes during development of CLP renal failure and to determine the effects of NOS inhibition (L-NAME) and 0.15 M NaCl administration on tail blood pressure and renal function in randomly assigned five groups (n = 10 each): (1) Sham-operated, (2) Sham-operated L-NAME-treated, (3) CLP rats, (4) CLP L-NAME-treated, and (5) CLP 0.15 M NaCl-treated rats. The basal tail blood pressure was not significantly different among the four groups. One week later, arterial pressure was significantly increased in sham-operated L-NAME-treated rats (159 +/- 12 mmHg) compare with the other groups (118 +/- 9.0 mmHg in nontreated rats, p < 0.05). Blood pressure shows a slightly and not significant decrease up to 12h in L-NAME and 0.15 M NaCl treated rats, which in turn was followed by a significant reduced arterial pressure 18h after CLP in both groups (L-NAME: 96.0 +/- 3.6 mmHg, p < 0.05) and NaCl: 82.3 +/- 2.4 mmHg, p < 0.05) compared to sham-operated groups. The glomerular filtration rate estimated by CCr decreases significantly in the CLP untreated group (p < 0.001) and did not significantly differ from the sham-operated and L-NAME-treated groups (p = 0.4) during the studies of renal tubule sodium handling. On the other hand, subcutaneous 0.15 M NaCl administration prevented CCr decreases in CLP rats (p = 0.25). CLP increased the FENa in the sham-operated from: 857.2 +/- 85.1 delta%min(-1) to CLP: 1197.8 +/- 119.0 delta%min(-1). The high FENa to CLP was blunted and significantly reduced by previous systemic treatment of animals with L-NAME from sham-operated+L-NAME: 1368.0 +/- 72.0 delta%min(-1) to CLP+L-NAME: 1148.0 +/- 60.4 delta%min(-1) (p < 0.01). The enhanced FENa in the CLP group were accompanied by a significant increase in proximal sodium reabsorption rejection. The salient findings of the present study suggest that a decrease in the blood pressure and creatinine clearance caused by CLP may benefit from L-NAM and fluid resuscitation during initial bacteremia (first 12 h) by promoting an additional increase of tubule sodium reabsorption in the post-proximal segments of nephrons, but these therapies could not prevent acute renal failure after established endotoxemia.
authors.affiliation: Faculdade de Medicina, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil.
authors.forename: Paulo
authors.initials: P
authors.lastname: César de Oliveira
authors.forename: Patricia Aline
authors.initials: PA
authors.lastname: Boer-Lima
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Figueiredo
authors.forename: José Antonio Rocha
authors.initials: JA
authors.lastname: Gontijo
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000201:enzymology*; D000704:Analysis of Variance; D000818:Animals; D001795:Blood Pressure Determination; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007677:Kidney Function Tests; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000503:physiopathology; D012965:Sodium Chloride / Q000494:pharmacology*
chemical_list: D012965:Sodium Chloride; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester