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Volume 12 Supplement 5

Sepsis 2008

Role of central nitric oxide on hormonal and cardiovascular alterations in experimental polymicrobial sepsis


Polymicrobial sepsis induced by cecal ligation and puncture (CLP) causes a massive nitric oxide (NO) synthesis and consequently several physiological alterations in cardiovascular and hormonal systems. Central NO is reported to modulate the secretion of vasopressin. Our aim was to study the central effect of an unspecific NO synthase inhibitor (L-NAME) on the mean arterial pressure (MAP), plasma nitrate levels (pNO), plasma arginine vasopressin concentration (pAVP) and hypothalamic arginine vasopressin mRNA content during polymicrobial sepsis induced by CLP.


Male Wistar rats received an intracerebroventricular injection of L-NAME (250 μg) or saline (vehicle) and 30 minutes later they were submitted to CLP or to a sham operation. Animals were decapitated 0, 4, 6, 20 or 24 hours after surgery and blood was collected for pNO and pAVP measurements. The brains were removed and the supraoptic and paraventricular nuclei were punched out for vasopressin mRNA determination by real-time PCR. In another set of animals the MAP was measured each 15 minutes 1 hour before and during 24 hours after surgery with intervals.


CLP caused an increase in pNO after 6 hours, and in pAVP at 4 and 6 hours, while the MAP decreased during 5 hours after surgery. Hypothalamic vasopressin mRNA showed a tendency to decrease in both nuclei. L-NAME pretreatment increased survival (80% versus 67%), blocked pNO increase and MAP decrease and also resulted in an increase in plasma vasopressin concentration in the initial phase of sepsis (P < 0.05). The vasopressin mRNA content increased at 20 and 24 hours in the paraventricular nucleus and only at 24 hours in the supraoptic nucleus.


These results demonstrate that central NO plays a role in blood pressure and in vasopressin synthesis and release during polymicrobial sepsis in rats.


Financial support from FAPESP.

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Oliveira-Pelegrin, G.R., de Azevedo, S.V. & Rocha, M.J.A. Role of central nitric oxide on hormonal and cardiovascular alterations in experimental polymicrobial sepsis. Crit Care 12, P33 (2008).

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  • Nitric Oxide
  • Vasopressin
  • Mean Arterial Pressure
  • Paraventricular Nucleus
  • Arginine Vasopressin