Soy-based diets reduce blood pressure in spontaneously hypertensive rats, but apparently not in hypertensive humans. In the present study, the antihypertensive potential of soy milk (500 mL twice daily) compared with cow's milk was investigated in a 3-mo double-blind randomized study of 40 men and women with mild-to-moderate hypertension. Before initiation of the study, urinary isoflavonoids (measured by HPLC) were undetectable in most cases (for genistein, they were always <100 micromol/L). After 3 mo of soy milk consumption, systolic blood pressure decreased by 18.4 +/- 10.7 mmHg compared with 1.4 +/- 7.2 mmHg in the cow's milk group (P < 0.0001), diastolic blood pressure decreased by 15.9 +/- 9.8 mmHg vs. 3.7 +/- 5.0 mmHg in the cow's milk group (P < 0.0001) and mean blood pressure decreased by 16.7 +/- 9.0 mmHg compared with 3.0 +/- 4.6 mmHg in the cow's milk group (P < 0.0001). Urinary genistein was strongly (r = -0.588) and significantly (P = 0.002) correlated with the decrease in blood pressure, particularly for diastolic values. In conclusion, chronic soy milk consumption had modest, but significant hypotensive action in essential hypertensive subjects. This hypotensive action was correlated with the urinary excretion of the isoflavonoid genistein.

Background-Reactive oxygen metabolites have been associated with gastrointestinal injury. Objective-To investigate whether mucosal reactive oxygen metabolites are involved in acid and pepsin induced oesophagitis, and if so, which specific metabolites. Methods-The effects of free radical scavengers and the anti-inflammatory drug ketotifen on rabbit oesophagitis induced by acidified pepsin were studied. Isolated oesophageal cells were obtained before and after oesophageal injury and the generation of superoxide anion and hydrogen peroxide was analysed by flow cytometry. The presence of inflammatory celis was determined by indirect immunofluorescence with a mouse antirabbit CDllb antibody. Results-Of the free radical scavengers tested, superoxide dismutase, which reacts with the superoxide anion, significantly reduced oesophagitis, whereas catalase, which reacts with hydrogen peroxide, had only a mild effect and dimethylsulphoxide had no effect. Ketotifen significantly reduced the inflammation and also prevented the induction of oesophagitis. Isolated cells obtained from the oesophageal mucosa after acidified pepsin exposure generated increased amounts of superoxide anions, which were mainly produced by CDl lb positive cells. Conclusion-Reactive oxygen metabolites, especially superoxide anion, produced by inflammatory cells play a significant part in the genesis of oesophagitis induced by acid and pepsin in rabbits and might be a target for future medical therapy.

SUMMARY1. The initial rate of Cd2+ uptake in human red cells was measured by atomic absorption spectrophotometry.2. About 96 % of Cd2" uptake was inhibited by DIDS (4,4'-diisothiocyanatostilbene-2, 2'-disulphonic acid) with IC50 (concentration giving 50% of maximal inhibition) of 0 3 /JM and by furosemide with IC50 of 500 /tM and was resistant to ouabain and amiloride. This indicates the implication of the [Cl--HC03-] anion exchanger in Cd21 uptake.3. DIDS-sensitive Cd2+ uptake required the presence of external HCO3. HC03-ions had a biphasic effect on Cd21 uptake. Low bicarbonate concentrations were stimulatory, suggesting formation of translocating bicarbonate-cadmium complexes. Higher bicarbonate concentrations were inhibitory, suggesting further bicarbonate complexation with formation of non-translocating species. Depending on the presence or absence of external Cl-, a maximal Cd21 uptake of 1P7 or 0 37 mmol (1 cells)-' h-' was observed at bicarbonate concentrations of 15 6 or 11 mm respectively.4. In the presence of bicarbonate, external Cl-ions strongly stimulated Cd2+ uptake, with linear increase between 70 and 125 mm. This suggests that one translocating species may have chloride as ligand.5. DIDS-sensitive Cd21 uptake was modestly inhibited by physiological concentrations of external phosphate and was resistant to external K+, Mg2+ and Ca2+.6. In conclusion, the anion exchanger is the major transport mechanism for red cell cadmium uptake. Translocating species appear to be monovalent anion complexes of cadmium with HC03-such as [Cd(OH) Knauf, 1987). In consequence, residual forms of operation of this exchanger may become important transport pathways for cations in the form of anionic complexes. For instance, Na+ can reach the red cell interior through the anion exchanger in the form of NaCO3-ion pairs (Becker & Duhm, 1978;Funder, Tosteson & Wieth, 1978;Garay, Hannaert, Nazaret & Cragoe, 1986). The importance of this NaCO3-influx is illustrated by the clinical observation that patients with MS 8766 M. LOU, R. GARAY AND J. 0. ALDA metabolic alkalosis, characterized by an increased HCO3-concentration in the plasma, accumulate Na+ in their erythrocytes (Funder & Wieth, 1974a, b;Funder, 1980). Recent studies have suggested that the anion carrier may play an important role in the uptake of those trace elements able to form complexes with bicarbonate, carbonate and/or chloride in significant amounts under physiological conditions: lead, probably in the form of a [PbCO3Cl]-anionic complex (Simons, 1986), zinc, probably in the form of a [Zn(HCO3)2Clf and/or [ZnOH(HCO3)Cl] anionic complex(es) (Kalfakakou & Simons, 1986Alda & Garay, 1989) (Alda & Garay, 1990). For several reasons it suggested to us that this could be the case for cadmium. First, Cl-or HC03-ions can associate with Cd2+ in order to form anionic complexes (Baes & Mesmer, 1976;Phillips & Silvester, 1983;Bernard & Busnot, 1984;Prince, 1987). Second, it has been previously shown that Cd2+ is able to be transported across red cell membranes, although the...

The initial rate of Cu2+ uptake in human red blood cells was measured by atomic absorption. About 80% of Cu2+ uptake was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) concentrations greater than 5-10 microM. DIDS-sensitive Cu2+ uptake required the presence of external HCO3- or external Cl-. Cl- strongly stimulated Cu2+ uptake following a Michaelis-like function, with apparent dissociation constant (KCl) of 72 +/- 9.4 (SD) mM (n = 6 experiments). HCO3- stimulated DIDS-sensitive Cu2+ uptake following a Michaelis-like function, with apparent dissociation constant (Kbic) of 10 +/- 1.9 (SD) mM (n = 4 experiments). Maximal rates (of Cl(-)- or HCO3(-)-stimulated Cu2+ uptake) were nonadditive. DIDS-sensitive Cu2+ uptake was not modified by physiological concentrations of phosphate or sulfate. Conversely, it was strongly inhibited by physiological concentrations of L-histidine and cysteine (at a Cu2+ concentration of 100 microM, these physiological ligands exhibited KHis and KCys of 50 and 80 microM, respectively). By using a copper-selective electrode, we found that at pH 7-7.4 copper is associated with OH-, particularly in the form of Cu(OH)2 complexes. In conclusion, the anion exchanger is the major transport mechanism for red blood cell Cu2+ uptake. The translocating species can be the monovalent anion complexes of copper with OH-, Cl-, and/or HCO3-.