Ricin induces glomerular thrombotic microangiopathy, closely resembling that which occurs in verocytotoxin-producing E. coli-induced HUS. As in HUS, high concentrations of proinflammatory cytokines are present, which are probably a result of cytokine superinduction by the toxin.

Plasma immunoreactive human atrial natriuretic peptide (Ir-ANP) levels were measured in eight patients with chronic renal failure who were volume-expanded and during treatment by sequential ultrafiltration and haemodialysis. One patient was studied at two separate treatment sessions. Plasma Ir-ANP levels were raised in all patients (mean +/- SE 184 +/- 44 pmol/l, n = 9) compared with healthy controls (11 +/- 1.4 pmol/l), but showed considerable inter-patient variability. Plasma Ir-ANP levels fell with fluid removal during ultrafiltration (123 +/- 30 pmol/l, n = 9, P less than 0.02) and again as fluid was removed during haemodialysis (76 +/- 20 pmol/l, n = 9, P less than 0.02). Seven patients studied 48 h later, before their next dialysis treatment, had regained weight and showed a coincident rise in circulating plasma Ir-ANP (130 +/- 33 pmol/l, n = 7). Our data would support the hypothesis that the secretion of ANP is determined by volume or by a stimulus related to volume. However, it does not exclude the possibility that a factor other than extracellular fluid volume expansion contributes to the raised plasma Ir-ANP levels in chronic renal failure.

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Objectives-To investigate the role of prostaglandins in maintaining circulatory homoeostasis in chronic heart failure and the hypothesis that an increase in vasodilatory prostaglandin synthesis may contribute to the actions of angiotensin converting enzyme inhibitors in heart failure. Design-Randomised, double blind, placebo controlled studies. Cardiac output and renal and limb blood flow were measured after oral indomethacin 50 mg or placebo followed by "open" intravenous infusion of prostaglandin E, (study A). In a second study the same measurements were made after oral indomethacin 50 mg or placebo was given 30 min before "open" captopril (study B). Methods-Blood pressure was measured using a mercury sphygmomanometer. Cardiac output was determined by Doppler interrogation ofblood flow in the ascending aorta and echocardiographic measurement of aortic root diameter. Renal blood flow was calculated from the effective renal plasma flow measured by p-aminohippurate clearance and the haematocrit, and glomerular filtration rate by endogenous creatinine clearance. Limb blood flow was measured by venous occlusion plethysmography using mercury in silastic strain gauges. The concentration of plasma prostaglandin E, was measured by radioimmunoassay. Prostaglandins are 21 carbon fatty acids synthesised from arachidonic acid by all body tissues including the kidney and vascular endothelium. Stimuli to prostaglandin production include ischaemia, catecholamines, angiotensin II, bradykinin, and vasopressin.' 2 Prostaglandins E2 and I2 are potent vasodilators and are thought to act locally to increase blood flow.2 Many of the factors known to stimulate prostaglandin synthesis are present in heart failure and circulating concentrations of metabolites of prostaglandins E2 and I2 are increased in some patients with heart failure.3 It has been suggested that vasodilatory prostaglandins have an important role in maintaining circulatory homoeostasis in heart failure when tissue perfusion is reduced.4 In parallel with the activation of nervous and humoral vasoconstrictor systems, increased prostaglandin synthesis may act as a "counter regulatory" mechanism to limit local vasoconstriction and maintain local blood flow. Uncontrolled studies have shown adverse renal and systemic haemodynamic effects after inhibition of prostaglandin synthesis in chronic heart failure.3 5Angiotensin converting enzyme and kininase II are structurally identical so that angiotensin converting enzyme inhibitors not only inhibit the renin angiotensin system but also inhibit the degradation of kinins. Bradykinin is a potent vasodilator and also a stimulus to the synthesis of prostaglandins.6 This pivotal position of the angiotensin converting enzyme means that angiotensin converting enzyme inhibitors not only inhibit the vasoconstrictor renin angiotensin system but may also facilitate the production of vasodilators such as bradykinin and prostaglandin.

Aluminium (Al) is absorbed from a variety of foodstuffs and medications. Its major route of elimination from the body is in the urine. However, current knowledge concerning its glomerular filtration and, more particularly, its reabsorption/secretion is fragmentary. Most (80–90%) of Al in the plasma is normally bound to protein (mainly transferrin) and is therefore unfilterable; the remainder is bound to low molecular mass compounds, of which citrate appears to be the most important. In vitro determinations using artificial membranes indicate that ∼10% of Al is filtered at normal plasma concentrations. However, when plasma Al is raised experimentally, its filterability falls, unless the excess Al is complexed with citrate; the aluminium citrate complex appears to be freely filtered. Information on tubular Al reabsorption at normal plasma concentrations is inconsistent. Filtered Al appears to be at least partially reabsorbed, although the reabsorptive mechanisms remain speculative. A consensus is emerging that elevated plasma Al concentrations result in a fall in fractional Al reabsorption, and a recent micropuncture study indicates that under these circumstances the only significant site of Al reabsorption is the loop of Henle.