BLOCKING nNOS DOES NOT AFFECT SURVIVAL RATE BUT MODIFIES THE HYDROELECTROLYTIC BALANCE IN EXPERIMENTAL SEPSIS

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Camila Henriques Coelho chcoelho@fcfrp.usp.br (1)  Gabriela Ravanelli de Oliveira Pellegrin (1), Thalita Freitas Martins (1), Maria José Alves da Rocha (2).

(1) Faculdade de Ciências Farmacêuticas de Ribeirão Preto (2) Faculdade de Odontologia de Ribeirão Preto – USP.

Introduction: Sepsis, the systemic response to severe infection, and its complication, the septic shock, show several physiological alterations that include changes in vasopressin secretion, hematocrit, refractory hypotension and hormone secretion. Experimental sepsis induced by cecal ligation and puncture (CLP) is the model that better mimes the clinical course of the sepsis because presents a polymicrobial infectious focus and shows a large complexity of the inflammatory response. The nitric oxide (NO) is a not-conventional neuromodulator, that is reported to be involved in neuroendocrine and hemodynamic mechanisms. During sepsis, the high production of NO contributes to the deleterious effects of this syndrome, causing alterations such as the increase of vascular permeability, loss of plasma protein, hypovolemia and  persistent hypotension. Recently a peripheral injection of 7-nitroindazole, a blocker of neuronal nitric oxide synthase (nNOS), was shown to reduce the NOS activity in the hypothalamus and the vasopressin secretion without modifying the hydroelectrolytic changes caused by salt loading. Objective: To evaluate the effect of the intraperitoneal injection of the 7-nitroindazole in the survival rate, the peripheral NO production and the hydroelectrolytic balance during experimental sepsis in rats. Methods: Male Wistar rats (250-300 g) were submitted to CLP or sham operation.  Thirthy minutes before the surgery, they were intraperitoneally injected with 7-nitroindazole (50mg/kg) or with vehicle (DMSO 10%/sesame oil, 1:9) as control. In one group the survival rate was analyzed for five days. In another group the animals were decapitated 0, 4, 6 and 18 h after surgery and blood was collected to analyse hematocrit, plasma osmolality, serum sodium, plasma protein and nitrate levels. Results: The drug did not change significantly the survival rate in rats submitted to the sepsis (p = 0,1403) The plasma osmolality and sodium did not show temporal alterations in both groups, vehicle or drug. The hematocrit increased 4 and 6h after CLP and the pretreatment with 7-nitroindazole recovered the volemia (p<0,05). The plasma protein levels show a decrease only 6h after the CLP and the 7-nitroindazole pretreatment antecipated this decrease at 4h (p<0,05).  The nitrate production increased only after 18h of CLP and the drug  administration anticipated this increase to 6h (p<0,05). Conclusion: Blocking the nNOS does not change the survival rate, osmolality and serum sodium but worsens the hypovolemia and the loss of protein and anticipate the production of nitric oxide in experimental sepsis.