Effects of chronic infusion of endotoxin on renal and cardiovascular function in rats

A study was made of the renal and cardiovascular responses of rats to the chronic intravenous administration of bacterial endotoxin. Endotoxin (E coli; 026: B6) was infused intravenously at the rate of 10 μg/h for a period of 4-6 days by means of subcutaneously implanted osmotic mini-pumps. The chronic endotoxemia resulted in a large fall in the renal output of sodium, a decrease in urine osmolality and an increase in potassium output. Aldosterone concentration in plasma was not changed. The renal retention of sodium was associated with an increased plasma volume, sodium space and total body exchangeable sodium. A study of renal function using clearance methods showed that the above changes occurred in the absence of statistically significant changes in glomerular filtration rate, renal plasma flow or filtration fraction. Measurements of renal medullary plasma flow by means of an isotope accumulation method indicated that no significant redistribution of intrarenal blood flow had occurred which might account for either the retention of sodium or the impaired renal concentrating ability. An investigation of cardiovascular function showed that rats with chronic endotoxemia had a significantly increased cardiac output as measured by the reference sample technique using radio-labelled plastic microspheres. These animals also had an increased stroke volume, bradycardia, hypotension and a decreased total peripheral resistance. The renal fraction of the cardiac output was significantly reduced but total renal blood flow was unchanged. The fractional distribution of nutritional blood flow to the kidney, as measured with ⁸⁶RbCl, was not significantly changed. Because of theoretical, but possible, sources of error inherent in the use of microspheres to measure cardiac output an attempt was made to confirm the above data using an alternative method. Measurement of cardiac output using the direct Fick method did not disclose a significant difference in cardiac output. Measurements were also made of the circulating half-life of endotoxin in plasma using ⁵¹Cr-labelled endotoxin. There was a very large increase in the rate of plasma clearance of endotoxin in rats subjected to chronic endotoxemia but no change in the fractional uptake of endotoxin by selected organs. It is suggested that the observed changes in renal function were secondary to the hemodynamic effects of endotoxin rather than to direct nephrotoxic effects.Medicine, Faculty ofCellular and Physiological Sciences, Department ofGraduat