Derivation of antihypertensive neutral renomedullary lipid from renal venous effluent.

: The ANRL was derived from the renal venous effluent as the kidney exerted its nonexcretory antihypertensive function. This was made possible by three developments: (1) improvement in the extraction of ANRL from fresh renal medulla; (2) the fact that purified ANRL caused an acute vasodepressor effect (acted as a vasodilator); and (3) experience with unclipping the one-kidney, one-clip hypertensive rat. Unclipping after an anastomosis between the ureter and the vena cava caused the MAP to return to normal levels in an average of 20 hr. At an average of 5 hr, when the MAP had dropped an average of 34 mm Hg (from approximately 190), an exchange infusion was started and blood was collected from the renal vein. The plasma was separated, lyophilized, and extracted for total lipids. The lipids were subjected to two TLC procedures and tested for vasodepressor activity. Renal venous effluent, under those conditions, yielded a considerable amount of vasodepressor lipid that was similar to that derived from fresh renal medulla. Controls (normal, nephrectomized, and hypertensive animals) yielded little or no such lipid. Indomethacin did not interfere with the derivation of the vasodepressor lipid. As the MAP was lowered and the ANRL-like lipid appeared in the renal venous blood, the RICs degranulated. The RICs appear to be the source of the antihypertensive lipid.