1. There is growing evidence that an impairment in the function of nitric oxide synthase may play a role in the vascular complications of diabetes mellitus. The relaxation of resistance arteries from the mesenteric and hindlimb circulations of streptozotocin-induced diabetic rats and age-matched controls were investigated using two endothelium-dependent vasodilators, bradykinin and acetylcholine, and the endothelium-independent vasodilator sodium nitroprusside. The contractile responses to the α 1 -adrenergic agonist phenylephrine were also studied. 2. Endothelium-dependent relaxation to acetylcholine was impaired in the diabetic rats in arteries from both mesenteric and hindlimb circulations (hindlimb pEC 50 , 7.93 ± 0.08 in the control compared with 7.38 ± 0.10 in the diabetic rat; mesenteric pEC 50 , 7.47 ± 0.04 in the control compared with 6.65 ± 0.06 in the diabetic rat; unpaired t -test P < 0.0001). Bradykinin elicited relaxation in only the mesenteric arteries, and this was not attenuated in the diabetic rats compared with controls. 3. Endothelium-independent relaxation to sodium nitroprusside was similar in the two circulations and was not abnormal in the diabetic rats. There was no significant difference in constrictor responses to phenylephrine between diabetic rats and controls in either the hindlimb or mesenteric arteries, in contrast to an earlier study in which we showed increased sensitivity to noradrenaline. 4. The diabetic rats therefore demonstrated a specific impairment of receptor-mediated endothelium-dependent relaxation to acetylcholine. These results suggest that, in this diabetic model, the ability of the endothelium to relax arteries via nitric oxide may involve a defect of a specific signal transduction pathway, leading to reduced production of nitric oxide.

1. Leucocyte Na + /H + exchange and intracellular pH were investigated in physiological buffer containing bicarbonate. 2. The amiloride analogue 5-( N,N -hexamethylene) amiloride (1 × 10 −5 mol/l), an inhibitor of Na + /H + exchange, had no significant effect on resting leucocyte pH, Na + influx or Na + content. 3. Ammonium chloride washout induced a profound intracellular acidosis, stimulating Na + /H + exchange. This led to a 236% increase in Na + influx. Eighty-eight per cent of this increase was inhibited by 5-( N,N -hexamethylene) amiloride. This demonstrates that 5-( N,N -hexamethylene) amiloride is an effective inhibitor of Na + /H + exchange in human leucocytes. 4. The recovery from intracellular acidosis was shown to be dependent entirely on the presence of extracellular Na + . The K i for inhibition by 5-( N,N -hexamethylene) amiloride of the recovery was 0.5 μmol/l. 5. Incubation with serum increased Na + influx and Na + content: the maximal effect was reached at 20% dilution. Serum (10%, v/v) increased influx by 40%, and 20% (v/v) serum by 102%, over resting levels. Only 43% of the serum-induced increase in Na + influx was inhibited by 5-( N,N -hexamethylene) amiloride. This represented one-fifth of total Na + influx. 6. Leucocyte intracellular pH increased on incubation with serum. This alkalinization was inhibited using 5-( N,N -hexamethylene) amiloride. 7. Studies of Na + /H + exchange in leucocytes in physiological and pathological states are more likely to reflect the state in vivo if carried out in the presence of autologous serum.

1. Endogenous digoxin-like immunoreactivity (EDLI) was measured in the serum of 85 normotensive pregnant (NTP) women and 77 women with pregnancy-induced hypertension (PIH) by a radioimmunoassay (New England Nuclear). All women were in the third trimester. 2. EDLI, which was undetectable in serum from nonpregnant women, was present in NTP and PIH and was significantly higher in PIH. EDLI correlated with gestational age in NTP, but not in PIH. 3. Ouabain-sensitive Na + transport was estimated in normal peripheral blood leucocytes after incubation with sera from 50 NTP and 42 PIH women. Significant inhibition of active Na + transport occurred only with the serum of hypertensive patients without proteinuria. 4. EDLI did not correlate with the effect of the sera on active Na + transport. The radioimmunoassay therefore provides a poor index of Na + transport inhibitory activity in PIH.

1. Endogenous digoxin-like immunoreactivity (EDLI) was measured by radioimmunoassay for digoxin in 13 paired samples of arterial and venous umbilical cord serum. EDLI was present in vein and artery, but was higher in the venous samples ( P < 0.025). 2. The venous cord serum inhibited the ouabain-sensitive sodium efflux rate constant of a normal mixed leucocyte population when compared with the effect of arterial cord serum ( P < 0.005). 3. It is suggested that the placenta may be involved in the production or metabolism of neonatal EDLI and of the inhibitor of sodium transport.

1. In confirmation of previous studies, serum obtained from cord blood demonstrated endogenous digoxin-like immunoreactivity (EDLI). Sera from pregnant women in the third trimester also demonstrated EDLI, which disappeared after delivery. 2. Cord serum inhibited the total sodium efflux rate constant of a mixed leucocyte preparation when compared with the effect of control serum. This inhibition resulted from a depression of the ouabain-sensitive (sodium pump) component of the rate constant. 3. An ultrafiltrate of the serum (mol. wt. < 30 000) also inhibited ouabain-sensitive leucocyte sodium transport when compared with filtrate obtained from control serum. 4. DHA-S Dehydroepiandrosterone sulphate (DHA-S) and cortisone, both present in high concentration in cord serum, demonstrated EDLI but did not affect leucocyte sodium transport in the cells of normal subjects. 5. DHA-S had no effect on sodium transport or vasoconstrictor activity in human omental resistance vessels. 6. It is concluded that EDLI of cord serum is associated with sodium transport inhibitory activity. This is unlikely to be attributable to DHA-S or cortisone.

1. Sodium efflux rate constants and intracellular sodium were measured in leucocytes from healthy volunteers in the presence and absence of the calcium antagonist verapamil hydrochloride. 2. Verapamil stimulated sodium pump activity and this effect was dependent on the presence of external calcium. 3. Verapamil has been reported to reverse the abnormality of sodium transport seen in leucocytes from patients with essential hypertension and the present study demonstrates that sodium pump activity in leucocytes from control subjects is also stimulated by exposure to verapamil in vitro. This direct cellular effect appears to be due to the calcium antagonist properties of the drug.

1. Leucocyte sodium transport was investigated as a possible assay for the small molecular weight natriuretic material isolated from the urine of normal subjects who had undergone volume expansion by saline infusion. 2. This fraction (fraction four or FIV), inhibitory to sodium transport in several other assays, was also found to inhibit leucocyte sodium transport. 3. FIV isolated from the urine of five normal subjects undergoing the natriuresis of mineralocorticoid ‘escape’ was also found to be inhibitory to leucocyte sodium transport. 4. Leucocytes isolated from the blood of the same subjects during mineralocorticoid escape showed decreased sodium transport.

1. The spectrum of transit times of sodium o -iodohippurate (Hippuran) through the kidney can be derived from an 131 I- (or 123 I-) labelled Hippuran renogram by deconvolution. In the rabbit and pig, as has previously been shown in man, the frequency distribution curve for the transit times was bimodal. Since the transit time is likely to be proportional to the nephron length, the area of the first mode is likely to represent plasma flow to the shorter outer cortical nephrons whereas the delayed mode represents flow to the long juxtamedullary nephrons. 2. This interpretation was tested by simultaneously comparing renography with the microsphere method of measuring intrarenal plasma flow distribution in 12 rabbits and two pigs with a variety of anaesthetics. A close agreement was found between both methods for the percentage of plasma flow distributed to the outer cortical nephrons, thus supporting the use of ‘transit renography’ to determine the intrarenal distribution of plasma flow.