Role of Nitric Oxide in Cardiovascular Responses to Endotoxemia in Neonatal Lambs

Abstract

To determine whether systemic cardiovascular responses to gram-negative endotoxemia are mediated by nitric oxide, we evaluated time-dependent changes in contractility and hemodynamics in a neonatal sheep model subjected to nitric oxide synthesis inhibition with L-Name (N^ω-nitro-L-arginine methyl ester). Four groups were studied: control (C), endotoxin (E), endotoxin L-Name where the nitric oxide synthase inhibitor was given prior to endotoxin (ELN), and a control L-Name group pretreated with L-Name (CLN). The contractility, measured as end-systolic elastance (Ees), increased transiently in the E group and then returned to baseline. In contrast, Ees declined over time in the ELN group. In terms of peripheral hemodynamics, both the E and ELN groups demonstrated significant progressive decreases in blood pressure and vascular resistance. The results of this study suggest that nitric oxide contributes to the newborn contractile response of the heart to endotoxin, but does not appear to mediate the systemic vascular relaxation response.

LPS induces cardiomyocyte injury through calcium-sensing receptor

“…However, the role of CaSR in LPS-induced myocardial dysfunction has yet not been fully defined. LPS is a major structural component of Gram-negative bacteria, and a key mediator of the body’s response to infection [21, 22]. LPS induces expression of pro-inflammatory cytokines, such as TNF-α and IL-6, which are involved in the pathogenesis of sepsis and are also an early predictors of organ dysfunction [23–25].…”