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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.