pituitrin and pimagedine

Clinical and experimental studies with LPS injection have shown an increase in vasopressin (AVP) secretion in the early phase of severe sepsis, which is subsequently reduced despite persistent hypotension. The aim of this study was to evaluate the role of inducible nitric oxide synthase (iNOS)-derived NO in hypothalamic activation and in AVP release during severe sepsis induced by cecal ligation and puncture (CLP). Male Wistar rats received i.p. injections of aminoguanidine, an iNOS inhibitor, or saline 30 min before CLP or sham surgeries (controls). CLP led to increased plasma nitrate levels, protein leakage and hypotension and caused mortality of 80% by 24 h. Expression of c-fos in paraventricular (PVN), supraoptic (SON) and organum vasculosum of lamina terminalis (OVLT) nuclei, as well as plasma AVP concentration were increased at 6 h but reduced to basal levels 24 h after CLP. Aminoguanidine pre-treatment prevented the increase in plasma nitrate levels and hypotension in the first 6 h. It also reduced AVP secretion and hypothalamic c-fos expression. After 24 h, the pre-treatment reduced plasma nitrate levels, protein leakage and caused a partial recovery of c-fos expression in SON and OVLT but did not affect AVP release. Furthermore, mortality was reduced to 43%. We conclude that during the early phase of severe sepsis hypotension caused by the iNOS-derived NO is partially responsible for the hypothalamic activation and AVP release. In the late phase, however, the iNOS-derived NO prevents brain activation blunting AVP secretion contributing to hypotension, irreversible shock and animal death.

Topics: Animals; Bacterial Infections; Blood Pressure; Drinking; Enzyme Inhibitors; Gene Expression Regulation; Guanidines; Hypothalamus; Immunohistochemistry; Male; Nitric Oxide; Nitric Oxide Synthase Type II; Osmolar Concentration; Proto-Oncogene Proteins c-fos; Radioimmunoassay; Rats; Rats, Wistar; Sepsis; Time Factors; Vasopressins

Septic shock is characterized by arteriolar vasodilation and hypotension. We have tested the hypothesis that nitric oxide arising from inducible nitric oxide synthase in the central nervous system is responsible for the deficiency in vasopressin release and consequent hypotension during experimental septic shock.. Septic shock was induced in male Wistar rats by intravenous injection of 1.5 mg/kg lipopolysaccharide. After lipopolysaccharide administration, we found a significant decrease in mean arterial pressure with a concomitant increase in heart rate, a significant decrease in diuresis, and a transitory decrease in body temperature. An increase in plasma vasopressin concentrations occurred in these animals and was present for 2 hrs after lipopolysaccharide administration, returning close to basal concentrations thereafter and remaining unchanged for the next 24 hrs. When lipopolysaccharide was combined with central administration of aminoguanidine, an inducible nitric oxide synthase inhibitor, we observed a sustained increase in plasma vasopressin concentration and in the maintenance of blood pressure at 4 and 6 hrs after lipopolysaccharide treatment compared with rats treated with lipopolysaccharide alone.. These data indicate that central nitric oxide arising from the inducible nitric oxide synthase pathway plays an important inhibitory role in vasopressin release during experimental septic shock and may be responsible for the hypotension occurring in this vasodilatory shock.

Topics: Animals; Central Nervous System; Enzyme Inhibitors; Guanidines; Hemodynamics; Hypotension; Lipopolysaccharides; Male; Nitric Oxide; Nitric Oxide Synthase; Rats; Rats, Wistar; Shock, Septic; Vasopressins

Topics: Animals; Enzyme Inhibitors; Guanidines; Humans; Nitric Oxide; Nitric Oxide Synthase; Rats; Shock, Septic; Vasoconstrictor Agents; Vasopressins