No abstract

1. The antihypertensive neutral renomedullary lipid (ANRL) is a natural product derived from fresh renal medulla and from venous blood. 2. ANRL appears to be an antihypertensive hormone secreted when the kidney exerts its antihypertensive function after unclipping. 3. The kidney appears to be the main source of ANRL, maintaining a basal rate of secretion of ANRL. 4. The kidney of the one-kidney, one-clip hypertensive rat appears to secrete an inappropriate amount of ANRL. Thus a deficiency of the secretion of the antihypertensive hormone may play a role in the pathogenesis of the one-kidney, one-clip hypertensive model. 5. Degranulation of the renomedullary interstitial cells (RIC) occurs as the kidney exerts its antihypertensive action after unclipping, supporting these cells as the source of ANRL. 6. Channels between collecting duct cells may encourage water reabsorption while the clip is in place; conversely, the closure of these channels when the clip is removed may encourage the diuresis that is observed.

SUMMARY Two types of biologically active lipids have been derived from renomedullary tissue. One is neutral (ANRL) and the other polar (APRL).117 These same tissues yield lipid substances that exert an antihypertensive action. 18"" During attempts to isolate the active principle of these lipid substances, two types of biologically active lipids have been derived ( fig. 1). By chromatographic and solubility characteristics, one is neutral (designated as the antihypertensive neutral renomedullary lipid or ANRL) 20 and the other is polar (designated as the antihypertensive polar renomedullary lipid or APRL). Upon a bolus I.V. injection of APRL into a one-kidney, one clip Goldblatt hypertensive rat (1KGH), a rapid and very sharp decline of the mean arterial pressure (MAP) occurs. The magnitude and duration of this depressor effect is dose-dependent. 23 When multiple doses of APRL are given to the same hypertensive animal the MAP remains depressed for 20 or more hours after the last dose."-u Thus, APRL evokes an acute and prolonged depressor effect, depending on the manner of its injection and the dose level. Given intravenously as a bolus dose, ANRL is attended by a lag period of 2 or more minutes and then the MAP declines slowly to a maximum after 15-60 minutes. An equal or longer period of time is required for the pressure to return to its previous level.The antihypertensive activity labeled APRL was discovered after attempts to improve the yield of ANRL. Two steps were added to the isolation procedure, namely a reduction step using the reducing agent Vitride (Na Al H, (OCHjOCH,),, Eastman organic chemicals)" followed by acetylation.These steps were included because of hints that ANRL might have a vinyl ether side group. 2 * Vitride presumably would not attack such linkage but would break ester bonds. 27 It was hoped that the methyl esters) would assist in subsequent purification steps. However, a second treatment with Vitride destroyed APRL activity (see Results and Discussion).