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Biomedical subjects

L Poston

Publications and source records attributed to L Poston.

At least 127 records · Page 7Linked to original sources
PubMed1991

Ouabain and responses to endothelium-dependent vasodilators in the human forearm.

Ouabain inhibits endothelium-dependent vascular relaxation in vitro, but has not been studied in this regard in vivo. We have therefore measured blood flow responses to carbachol, bradykinin and sodium nitroprusside (endothelium-dependent and endothelium-independent vasodilators) infused into the brachial artery with and without co-infusion of ouabain (2 micrograms min-1). Six healthy male volunteers were each studied on two occasions. Ouabain reduced basal forearm blood flow, by 18.0 +/- 4.1% (mean +/- s.e. mean, 2P less than 0.05), but had no significant effect on responses to any of the three vasodilators. These results indicate that effects of ouabain on endothelium-dependent relaxation in vitro must be interpreted with caution.

Adult↗
PubMed1990

Sodium transport inhibitors in pregnancy-induced hypertension.

In blacks and whites of similar socioeconomic background, the incidence of pregnancy-induced hypertension (PIH) is probably the same. In underdeveloped countries, however. PIH is often a life-threatening complication of pregnancy. Recent theories as to the etiology of PIH include the suggestion that vascular tone may be increased as a result of inhibition of active sodium transport in vascular smooth muscle. This may be the result of an inhibitor of sodium transport present in the serum. The literature concerning the demonstration of endogenous sodium transport inhibitors and endogenous digoxinlike immunoreactivity (EDLI) in PIH is reviewed and discussed.

Biological Transport, Active↗
PubMed1990

A longitudinal study of maternal digoxin-like immunoreactive substances in normotensive pregnancy and pregnancy-induced hypertension.

The serum of women in the third trimester of pregnancy demonstrates cross-reactivity with some commercially available antibodies to digoxin. A number of studies have suggested that levels of this digoxin-like immunoreactive substance(s) are further increased in patients with pregnancy-induced hypertension, and some have proposed that the digoxin-like immunoreactive substance could be useful as a predictor of pregnancy-induced hypertension. We measured digoxin-like immunoreactive substance levels every 2 weeks throughout the third trimester in 170 women; of these, 20 developed hypertension. Digoxin-like immunoreactive substance levels rose with gestational age. A graph of the slope of digoxin-like immunoreactive substance plotted against gestational age was fitted for the results obtained from each woman. There was no significant difference in the mean rate of increase of digoxin-like immunoreactive substance level per week between pregnancy-induced hypertension and normotensive pregnancy, nor was there any difference between these two groups at any gestational age studied. These results suggest that measuring digoxin-like immunoreactive substance levels is not useful as a predictor of pregnancy-induced hypertension.

Blood Pressure↗
PubMed1990

Effect of NG-monomethyl-L-arginine on endothelium-dependent relaxation of human subcutaneous resistance arteries.

1. Using a myograph to measure isometric tension, we have looked at the action of NG-monomethyl-L-arginine on the endothelium-dependent relaxation of human subcutaneous resistance arteries. 2. NG-Monomethyl-L-arginine, the novel inhibitor of endothelium-derived relaxing factor synthesis, caused concentration-dependent but only partial inhibition of maximal relaxation induced by acetylcholine in human subcutaneous resistance arteries. 3. The inhibitory action of NG-monomethyl-L-arginine on acetylcholine-induced maximal relaxation was partially reversed by incubation of the arteries in equimolar concentrations of L-arginine and NG-monomethyl-L-arginine. Subsequent incubation in L-arginine led to further reversal, but this was no greater than with incubation in physiological saline. 4. A component of acetylcholine-induced relaxation was sensitive to indomethacin, suggesting that this response is mediated by prostanoids as well as by endothelium-derived relaxing factor. 5. NG-Monomethyl-L-arginine did not increase the tension of resting human subcutaneous resistance arteries. NG-Monomethyl-L-arginine did enhance the contractile response to noradrenaline, possibly due to inhibition of release of endothelium-derived relaxing factor resulting from stimulation of alpha 2-adrenoreceptors on the endothelial cells.

Acetylcholine↗
PubMed1990

Effect of autologous serum on human leucocyte Na+/H+ exchange and intracellular pH.

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 x 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 Ki for inhibition by 5-(N,N-hexamethylene) amiloride of the recovery was 0.5 mumol/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.

Amiloride↗
PubMed1990

Cyclosporin A inhibits endothelium-dependent, prostanoid-induced relaxation in human subcutaneous resistance vessels.

The effect of cyclosporin on endothelium-dependent relaxation of human subcutaneous resistance vessels was investigated. Resistance vessels were obtained from normal subjects undergoing routine surgery. Acetylcholine-induced relaxation was shown to consist of at least two components, one mediated through vasodilatory prostanoids, the other through endothelium-derived relaxing factor (EDRF). Incubation with cyclosporin inhibited endothelium-dependent relaxation, as assessed by the response to acetylcholine. The inhibitory effect of cyclosporin on the acetylcholine response was most marked in the presence of methylene blue, which is an inhibitor of EDRF. This suggests that the inhibition of endothelium-dependent relaxation by cyclosporin is mediated by an effect on vasodilatory prostanoids.

Acetylcholine↗
PubMed1990

The rate of rise of corticotrophin releasing factor and endogenous digoxin-like immunoreactivity in normal and abnormal pregnancy.

Maternal plasma concentrations of corticotrophin releasing factor (CRF) and endogenous digoxin-like immunoreactivity (EDLI) were estimated in 80 normal and 88 abnormal pregnancies which were sampled sequentially from 24 weeks gestation to delivery. A slope was fitted for each woman's antenatal EDLI and CRF values, both of which rose significantly during gestation, and the mean of the slopes for the normal and abnormal groups for each value compared. There was no evidence of significant mean differences between groups for EDLI but there was evidence of a significant mean difference for CRF (P less than 0.05). After adjustment for other variables which may affect pregnancy outcome, the slopes for CRF were found not to be significantly related to outcome.

Corticotropin-Releasing Hormone↗
PubMed1990

Effects of ouabain and low sodium on contractility of human resistance arteries.

Earlier work with rat arteries has resulted in a widely held assumption that resistance artery smooth muscle will not contract on exposure to a reduced transplasmalemmal sodium gradient. In view of the well-recognized low sensitivity of rat tissue to cardiac glycosides, we have investigated the effects of altering the transplasmalemmal sodium gradient on vascular smooth muscle tone by using human resistance arteries. Incubation of arteries in low sodium or in ouabain to inhibit active sodium efflux for 1 hour increased the contractile response to caffeine stimulation; this finding indicated enhanced calcium buffering by the sarcoplasmic reticulum. Prolonged incubation in ouabain in the presence of phentolamine or diltiazem resulted in a concentration-dependent increase in the tone of resting human resistance arteries. Reduction of the transplasmalemmal sodium gradient by incubation in low sodium buffer effected an increase in tone similar to that obtained in the presence of ouabain. These results suggest that alteration of the transplasmalemmal sodium gradient may increase the vascular smooth muscle tone of human resistance arteries by altering intracellular calcium handling. This is a new finding in human resistance arteries and may involve inhibition and, indeed, reversal of sodium-dependent calcium efflux. A concentration-dependent potentiation of tone was found after the addition of ouabain to submaximally activated arteries. Sodium-calcium exchange may also play a pivotal role in this mechanism.

Arteries↗
PubMed1989

Serum digoxin-like substances in pregnancy-induced hypertension.

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 non-pregnant 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.

Biological Transport, Active↗
PubMed1989

Cyclosporine A inhibits relaxation but does not induce vasoconstriction in human subcutaneous resistance vessels.

The effects of cyclosporine on the functional characteristics of human subcutaneous resistance vessels were investigated. Resistance vessels were obtained from normal subjects undergoing routine surgery. Incubation with cyclosporine did not alter the resting tone of the vessels, but decreased the maximum contractile response and the sensitivity of the vessels to stimulation with exogenous noradrenaline and potassium. Cyclosporine decreased the rate of spontaneous relaxation and inhibited endothelium-dependent relaxation as assessed by the response to acetylcholine. Paradoxically, endothelium-independent relaxation as assessed by the response to sodium nitroprusside was augmented. Hypertension induced by cyclosporine may, in part, be explained by a reduction in relaxation of peripheral resistance vessels.

Cyclosporins↗
PubMed1989

Endothelin-induced contraction of human peripheral resistance vessels is partly dependent on stimulation of sodium-hydrogen exchange.

The role of Na-H exchange in endothelin-induced contraction of human peripheral resistance vessels was investigated. Endothelin produced a dose-dependent contraction which was greatly attenuated in the presence of a low extracellular sodium concentration. Inhibition of Na-H exchange by the amiloride analogue 5-(N,N-hexamethylene) amiloride (5-NNHA) resulted in a greater than 65% relaxation of a maximal endothelin-induced contraction in the presence of normal extracellular sodium. However, in the presence of a low extracellular sodium concentration, inhibition of Na-H exchange only resulted in a 25% relaxation. These data suggest that endothelin-induced vasoconstriction of human peripheral resistance vessels is mediated in part by stimulation of Na-H exchange.

Amiloride↗
PubMed1988

A comparison of endogenous digoxin-like immunoreactivity and sodium transport inhibitory activity in umbilical arterial and venous serum.

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 less than 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 less than 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.

Biological Transport, Active↗
PubMed1987

Evidence for an inhibitor of leucocyte sodium transport in the serum of neonates.

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. less than 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.

Biological Transport↗
PubMed1985

Sodium pump activity in thymocytes of rats with Goldblatt hypertension.

Sodium transport has been studied in thymocytes of one-kidney, one-clip (1K, 1C) and two-kidney, one-clip (2K, 1C) models of hypertension in the rat. No differences of intracellular sodium or sodium transport could be demonstrated in either model when compared with sham-operated controls. The experiments provide no evidence to support the concept that an inhibitor of sodium transport is associated with the development of hypertension in the one-kidney, one-clip rat. A previously unrecognized effect of incubation time and cell density on thymocyte sodium metabolism is reported.

Animals↗