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WE describe here the release from the kidney by angiotensin II and noradrenaline of substances which have the properties of prostaglandins. This observation may help to account for the antihypertensive function of the kidney first suggested by Fasciolo1, who demonstrated that removal of the kidney contralateral to an ischaemic kidney produced sustained hypertension in dogs. We have adapted the bioassay method of Vane2, the super-fused blood-bathed organ technique, for the detection of prostaglandins in renal venous blood in response to infusions of arigioteiisin II or noradrenaline into the renal artery.

Noradrenaline releases prostaglandins in the kidney, and in rats these augment rather than reduce vasoconstriction produced by the amine. Homogenates of kidneys of New Zealand rats inbred for hypertension exhibit lower prostaglandin inactivation by 15-hydroxydehydrogenase than controls. At the same time, augmentation of noradrenaline vasoconstriction by the released prostaglandin is exaggerated. This biochemical defect could be the inherited abnormality primarily responsible for the development of hypertension in these animals.

STIMULATION of the splenic nerves releases prostaglandins from the spleen to give concentrations of as much as 0.2 µg/ml. in splenic venous blood1. The release of prostaglandins might influence organs remote from the site of release, for prostaglandins can exert potent actions on smooth muscle2. The lung has recently been shown to determine the fate of many vasoactive substances; some are activated—conversion of angiotensin I to angiotensin II (ref. 3)—and some inactivated. The degree of inactivation seems to be specific for a given substance, ranging from almost complete (bradykinin4, 5-hydroxytryptamine5, prostaglandins E1 E2 and F2α (ref. 1)), to minor (noradrenaline6), to allowance of their free passage (adrenaline6 and angiotensin II (ref. 7)). The removal of prostaglandins by the lung restricts their activities to the organs from which they are released and between their organ of origin and the site in the pulmonary circulation where they are inactivated1. A prostaglandin which passed through the lungs after its release from an organ could be considered a circulating hormone, as long as it is not rapidly degraded in the blood. Ferreira and Vane1 reported that prostaglandins E1 E2 and F2α were stable in blood, though rapidly inactivated by the lung. Removal of prostaglandins A1 and A2 by the lung was not determined because the assay organs are insensitive to them. Vascular smooth muscle, however, unlike other smooth muscle, is reactive to low concentrations of prostaglandins A1 and A2 (refs. 8–10) and the renal vasculature is probably most sensitive to prostaglandins A1 and A2 (refs. 10 and 11). Because the renal vasculature is also sensitive to prostaglandins E1 and E2 (ref. 12), it has been used as an index of the fate of prostaglandins infused into the venous and arterial circulations.