Endotoxin releases a precursor to vasodilation from large veins in an NF-κB-dependent manner
Journal of Surgical Research(2004)
Abstract
Our previous studies have shown that when a segment of rat aorta was placed upstream and in series to a rat cremasteric isolated arteriole, endotoxin (ET) exposure produced significant vasodilatation. Without the aorta, no loss of tone was noted, indicating that a precursor, as of yet unidentified, was washed downstream, thereby inducing vasodilation. Prior treatment of the donor of either the aorta or the arteriole with pyrrolidine dithiocarbamate (PDTC), a potent NF-kappaB inhibitor, prevented the loss of tone. This suggests a role for NF-kappaB in the signaling pathway. The aim of this study was to determine if a large vein was also capable of releasing a similar factor in response to ET.This project followed the same experimental design except that the upstream aortic segment was replaced by a segment of vena cava. Male Sprague-Dawley rats were given an intraperitoneal (ip) injection of PDTC (100 mg/kg) or a sham injection of saline. First-order cremasteric arterioles were isolated, cannulated, and pressurized. A segment of inferior vena cava was then placed in series with the microvascular preparation. Arterioles were allowed to equilibrate and achieve spontaneous myogenic tone in a bath of warm physiological buffer over 1 h (t = 0). Internal vessel diameters were measured with video calipers and the response to ET or continued infusion of buffer was measured over 2 h (t = 120). The control group (n = 8) received a sham injection and the vessels were exposed to buffer only. The ET group (n = 7) was exposed to ET only. The PDTC group (n = 5) received PDTC only. The PDTC/ET group (n = 6) received PDTC and was exposed to ET.After equilibration, spontaneous tone (measured as a percentage of maximal diameter) was similar in the four groups (t = 0). After 2 h (t = 120), the ET group had significantly less tone (30.1 +/- 3.6%; P < 0.05) than the control (44.8 +/- 2.6%), the PDTC group (43.0 +/- 1.3%), and the PDTC/ET group (49.4 +/- 3.0%).These results show that the vena cava is capable of releasing a factor leading to vasodilation in response to ET in a manner similar to the aorta. Produced by the veins, it will affect venous capacitance as well as contribute to the total amount in the plasma pool affecting the tone of the resistant arterioles. Thus, it appears that these large conducting vessels, regardless of origin, play a role in the deleterious effects during septic events.
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Key words
PDTC,NF-κB,vena cava,sepsis,isolated arteriole,endotoxin
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