Effect of splenic extract on plasma volume and renal function in the rat

A hypotensive and natriuretic factor has recently been extracted from the rat spleen. Experiments were designed to investigate the mechanisms underlying the increase in urine output caused by splenic extract. Rat spleens were homogenized in phosphate buffered saline (PBS), centrifuged, subjected to ultrafiltration (mol. wt. cutoff 10,000), extracted on C18 affinity columns and dried. After reconstitution in isotonic saline, the extract was injected IV into conscious rats. Splenic extract caused a decrease in plasma volume (17.4+/-1.1 to 15.8+/-1.0 ml at 1 hr), and a delayed increase in urine output (1.8+/-0.2 to 4.0+/-0.4 ml/hr at 2 hr). There were no such changes in the muscle-injected control group. The increase in urine output was accompanied by an increase in glomerular filtration rate (splenic extract, 2.2+/-0.2 to 5.9+/-1.6 ml/min; muscle extract, 2.9+/-0.4 to 3.1+/-0.6 ml/min). Renal blood flow in the splenic extract-injected group fell during the course of the experiment so that, at 120 min., it was significantly lower both with respect to its baseline value and the muscle control group (splenic extract 22.1+/-0.2 to 17.5+/-2.2 ml/min; muscle extract 24.4+/-4.1 to 23.3+/-3.8 ml/min). During this same period, mean arterial pressure in the splenic extract group also fell from 98+/-2 to 91+/-4 mmHg. Renal vascular conductance therefore did not change. In conclusion, splenic extract causes a primary decrease in plasma volume and a delayed increase in urine output that is mediated, at least in part, by an increase in glomerular filtration rate. It is suggested that the splenic factor(s) probably achieves this by differential vasodilatation of the afferent glomerular arteriole and constriction of the efferent glomerular arteriole.