A. A. van Lambalgen

Effects of endotoxin on tone and pressure-responsiveness of Preglomerular juxtamedullary vessels

Endotoxin might affect renal vasoreactivity, but in vivo this is difficult to assess (systemic influences). Therefore, we used the in vitro blood-perfused juxtamedullary nephron preparation to study early changes in preglomerular vascular reactivity induced by exposure to endotoxin. Pressure-evoked vasomotor responses were determined videometrically by measuring steady-state inside vessel diameters at a perfusion pressure of 60 or 120 mmHg. Intraluminal application of endotoxin (primary contact with endothelium) for 120 min elicited an early (within 30 min) and sustained ∼25% vasoconstriction from arcuate artery to the distal portions of the afferent arterioles; autoregulatory responses, indicated by pressure-induced vasoconstriction, were unchanged. When topically applied, endotoxin (primary contact with smooth muscle cells) had no vasomotor effects. Significant constrictions, and increases in autoregulatory responses were obtained when the preparation was taken from kidneys from endotoxin-treated rats. Endotoxin had no effect on efferent arteriolar dimensions. Such preferential preglomerular early vasoconstriction is consistent with the early increase in renal resistance and parallel decrease in renal blood flow and glomerular filtration observed during endotoxin shock in vivo. Our results support the concept of local, endothelium-mediated effects of endotoxin on renal vessels.

The effect of mild endotoxemia during low arginine plasma levels on organ blood flow in rats

Objective Arginine is the sole precursor in the generation of the vasodilating agent nitric oxide. Arginine plasma levels are low in situations associated with endotoxemia such as major trauma, sepsis, and experimental obstructive jaundice. The aim of the study was to evaluate hemodynamics at low arginine plasma levels during a low-grade endotoxemia. Design Randomized, placebo-controlled animal laboratory investigation. Subjects Male Wistar rats (n = 29), anesthetized. Interventions Rats were randomly assigned to receive (at t = 0 mins) an intravenous infusion of 1.5 mL of 0.9% NaCl (SAL, n = 12) or 1.5 mL of an arginase (3200 IU) solution (ASE, n = 17) over a 20-min period. After the SAL or ASE infusion, rats were randomly assigned to receive an intravenous endotoxin (lipopolysaccharide [LPS], 150 &mgr;g/kg in 1.0 mL of 0.9% NaCl; ASE/LPS, n = 10 and SAL/LPS, n = 6) challenge or a control infusion (1.0 mL of 0.9% NaCl; ASE/SAL, n = 7 and SAL/SAL, n = 6) at t = 30 mins. Measurements and Main Results Organ blood flow was measured at t = 270 mins, using radiolabeled microspheres. At this time point, arginine plasma levels were lower in the ASE-treated rats (ASE/SAL vs. SAL/SAL and ASE/LPS vs. SAL/LPS, both p < .005, respectively). Cardiac output, mean arterial pressure, and therefore total peripheral resistance were similar for all groups. In the LPS-treated animals (SAL/LPS and ASE/LPS), cardiac output was maintained by a higher heart rate compensating the lower stroke volume. Organ blood flow to the small intestine and splanchnic blood flow was lower in the ASE/LPS-treated rats (both p < .05 when compared with other groups). Total liver blood flow was similar for all groups; the lower splanchnic blood flow was compensated for by a higher hepatic arterial blood flow. Conclusion The present study shows that low arginine plasma levels do not influence organ blood flow, whereas, during a low-grade endotoxemia, low arginine plasma levels result in reduced blood flow to the small intestine.