Plasma and Tissue Levels of Neuropeptide Y in Experimental Septic Shock: Relation to Hemodynamics, Inflammation, Oxidative Stress, and Hemofiltration

Abstract

Neuropeptide Y (NPY), a potent vasoconstrictor released from the sympathetic nerves, has been suggested to counterbalance sepsis-induced vasodilation. Thus, the changes in plasma and tissue NPY concentrations in relation to hemodynamic variables and inflammatory markers in a porcine model of moderate septic shock were investigated. Susceptibility of NPY to be removed by continuous hemofiltration in two settings has been also studied. Thirty-four domestic pigs were divided into five groups: (i) control group; (ii) control group with conventional hemofiltration; (iii) septic group; (iv) septic group with conventional hemofiltration; and (v) septic group with high-volume hemofiltration. Sepsis induced by fecal peritonitis continued for 22 h. Hemofiltration was applied for the last 10 h. Hemodynamic and inflammatory parameters (heart rate, mean arterial pressure, cardiac output, systemic vascular resistance, plasma concentrations of tumor necrosis factor-α, interleukin-6, and NPY) were measured before and at 12 and 22 h of peritonitis. NPY tissue levels were determined in the left ventricle and mesenteric and coronary arteries. Sepsis induced long-lasting increases in the systemic NPY levels without affecting its tissue concentrations. Continuous hemofiltration at any dose did not reduce sepsis-induced elevations in NPY plasma concentrations, nor did it affect the peptide tissue levels. The increases in NPY systemic levels were significantly correlated with changes in the systemic vascular resistance. The results support the hypothesis of NPY implication in the regulation of the vascular resistance under septic conditions and indicate that NPY clearance rate during hemofiltration does not exceed the capacity of perivascular nerves to release it.

A Dormant Microbial Component in the Development of Preeclampsia

“…It is also raised in sepsis, where it is considered to counterbalance the vasodilation characteristic of septic shock [e.g., Ref. (821, 822)]. The apparent paradox of a raised BP in PE and a lowered one in septic shock is considered to be related to the very different concentrations of endotoxin involved (Figure 7).…”

A Dormant Microbial Component in the Development of Pre-Eclampsia1

“…It is also raised in sepsis, where it is considered to counterbalance the vasodilation characteristic of septic shock (e.g. [762; 763]). The apparent paradox of a raised BP in PE and a lowered one in septic shock is considered to be related to the very different concentrations of endotoxin involved (Fig 7).…”

DPP4 Inhibition, NPY1-36, PYY1-36, SDF-1α, and a Hypertensive Genetic Background Conspire to Augment Cell Proliferation and Collagen Production: Effects That Are Abolished by Low Concentrations of 2-Methoxyestradiol

“…This, we felt, would model the in vivo condition in which several factors combined can have biologically, and possible clinically, meaningful effects that are much larger than the effects of any one given factor. Here we chose 3 nM because with all three peptides, this concentration provides a threshold stimulation of cell growth in WKY cells (Zhu et al, 2015b;Jackson et al, 2017) and approximates achievable in vivo tissue levels of NPY 1-36 , PYY 1-36 , and SDF-1a (Schmidt et al, 2005;Kuncová et al, 2011;Roux et al, 2012). The fact that we were able to detect significant effects at these low concentrations speaks to the potency and likely in vivo importance of these peptides in stimulating cellular activity, particularly when combined with additional treatment conditions.…”

“…We used concentrations of NPY 1-36 , PYY 1-36 , and SDF-1a of 3 nM because with all three peptides, this concentration provides a low (just above threshold) stimulation of cell growth in WKY cells (Zhu et al, 2015b;Jackson et al, 2017). Also, the concentration of 3 nM approximates achievable in vivo tissue levels of NPY 1-36 , PYY 1-36 , and SDF-1a (Schmidt et al, 2005;Kuncová et al, 2011;Roux et al, 2012).…”