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Biomedical subjects

G S Stokes

Publications and source records attributed to G S Stokes.

At least 37 records · Page 2Linked to original sources
PubMed1991

Effects of 17 alpha-ethinyl oestradiol in vitro on erythrocyte cation transport in men and women.

The effects of 17 alpha-ethinyl oestradiol in vitro upon erythrocyte Na(+)-K+ cotransport were investigated in nine normal males and in eight normal females during the mid-follicular phase of the menstrual cycle. At a concentration of 10(-1) mmol/l, Na(+)-K+ cotransport was almost completely inhibited. At concentrations of 10(-12) to 10(-2) mmol/l, a minor concentration-related effect was observed in males but not females. In the same concentration range, there was a significant difference in Na(+)-K+ cotransport between sexes. Thus, erythrocyte Na+K+ cotransport is lower in females than males, probably due to chronic exposure of their erythrocytes to endogenous oestrogen.

Adult↗
PubMed1990

The pharmokinetics of isradipine in hypertensive subjects.

In conjunction with a multicentre clinical trial of the calcium antagonist isradipine in hypertension, pharmacokinetic and pharmacodynamic studies were conducted in 9 subjects. An initial dose of 5 mg (capsule formulation) of isradipine was given orally. The mean Cmax, tmax and AUC(0-8) were 6.0 ng.ml-1, 1.5 h and 15.1 h.ng.ml-1 respectively. Seven subjects repeated the study at steady state after 10 week's dose titration with isradipine. Cmax, tmax and AUC(0-8) were 3.7 ng.ml-1, 1.2 h and 12.2 h.ng.ml-1 respectively indicating that the drug does not accumulate over time. Control of blood pressure paralleled plasma isradipine concentrations which suggested that the drug should be given at least twice daily. Pharmacokinetic studies performed in conjunction with clinical trials can provide valuable information about the patterns of drug response.

Adult↗
PubMed1990

Effect of dialysis on circulating Na,K ATPase inhibitor in uremic patients.

Deproteinized plasma from patients with renal failure had an inhibitory effect on Na,K ATPase activity measured in vitro by a linked-enzyme assay. No inhibitory effect was observed with plasma from normal subjects or from patients undergoing chronic ambulatory peritoneal dialysis. The inhibition of Na,K ATPase whether measured by the linked-enzyme assay or by 86Rb uptake in guinea pig aortic strips was decreased acutely by a single hemodialysis treatment, but was unaffected during a time-control study or ultrafiltration. Changes in Na,K ATPase activity and in Rb uptake were correlated, indicating that the presence of the enzyme inhibitor in uremic plasma was associated with depressed Na pump activity. Change in inhibition of Na,K ATPase activity did not correlate with change in body weight. Dialysis in vitro against a membrane of molecular weight 3,500 cut-off decreased the inhibitory effect of uremic plasma on Na,K ATPase. It was concluded that a dialyzable, low-molecular-weight Na,K ATPase inhibitor circulates in uremia but has no demonstrable role in volume homeostasis.

Adult↗
PubMed1990

Timing of blood pressure measurements in determining anomalies in duration of effect of an antihypertensive drug: assessment of isradipine.

Analysis of an antihypertensive drug trial, which involved measurements of blood pressure (BP) during visits to the clinic at a set time of day, showed that the initial dosage titration procedure had been inadequate in some patients. Plasma drug concentration-time curves and corresponding BP values suggested that control of BP was closely related to plasma drug concentration and that the duration of drug effect was shorter than the dosage interval of 12 h. This interpretation was supported by measurements of BP and drug concentrations taken at steady state, before and 2 h after taking the drug. Measurements of ambulatory BP revealed that some patients whose doses had been titrated at peak plasma drug concentrations had high BP at the time of trough plasma drug concentrations, whereas some of those titrated at trough times were hypotensive at peak times. Adjustment of antihypertensive therapy should entail observations of BP at times coincident with both peak and trough concentrations of the drug concerned, and can be facilitated by ambulatory BP monitoring.

Adult↗
PubMed1990

Optimum drug treatment in hypertension.

The ultimate objective in treating hypertension is to select an agent directed at the specific mechanism causing blood pressure elevation in the individual case. Such a choice is not possible in most cases at present; it is usually more important to match the profile of drug activity to the characteristics of the patient. In combination therapy, it is important also to match drug with drug, so as to obtain synergistic actions and to avoid adverse interactions. Finally, drugs that allow once-daily dosing are advantageous. These principles are used in deriving an optimum approach for practical application of the antihypertensive drug armamentarium available in 1990.

Antihypertensive Agents↗
PubMed1989

Comparison of the immediate and long-term effects of captopril and isosorbide dinitrate as adjunctive treatment in mild heart failure.

1. The efficacy of captopril and isosorbide dinitrate (ISDN) as adjunctive therapy to digoxin and diuretics in mild heart failure was compared in a double-blind study. 2. Twenty-one patients were randomly allocated to captopril (twice or three times daily) or ISDN. Eighteen patients completed a protocol of placebo run-in, dose titration and maintenance treatment for 3 months. 3. Symptom-limited exercise tolerance, ejection fraction and radionuclide indices of diastolic function estimated by gated blood pool scan did not change with either treatment. 4. Captopril improved functional class (Canadian Cardiovascular Society) and reduced requirements for increased diuretic dosage at both 1 and 3 months of maintenance treatment. Patients treated with ISDN required increased diuretic and did not improve their functional class. Differences between the treatments were significant only for diuretic dosage requirements. 5. We conclude that adjunctive therapy of mild heart failure with captopril administered twice daily provides a diuretic-sparing effect and may improve functional class during 3 months of maintenance treatment.

Blood Pressure↗
PubMed1989

Life history prototypes in the study of human individuality.

Using biographical data collected in late adolescence and young adulthood, prototypes or subgroups of individuals with similar patterns of prior behaviors and experiences were empirically identified. The prototypes are described, and the pathways taken by the prototypes from adolescence to adulthood are examined. Focusing on the various pathways or trajectories followed by different prototypes, we discuss implications of prototype membership for continuity and change in personality.

Achievement↗
PubMed1989

The effects of oestradiol administration on blood pressure and erythrocyte Na+ influx in oophorectomized rats.

The effects of oestrogen on blood pressure and erythrocyte Na+ influx were measured in oophorectomized rats treated with oestradiol benzoate (100ug/kg/week i.m.) or vehicle for eight weeks. A significant increase in mean blood pressure was observed in the oestradiol-treated compared to the vehicle-treated group, together with a significant increase in red cell [Na+]. Oestradiol administration produced no significant changes in total Na+ influx, cotransport, countertransport or Na+ diffusion and did not alter plasma [Na+], red cell [K+], mean corpuscular haemoglobin concentration (MCHC) or blood volume per 100g body weight. However, significant decreases in body weight, haematocrit and plasma [K+] were observed in the oestradiol-treated group. These results support previous observations that oestradiol increases blood pressure and suggest that chronic administration of oestrogen increases red cell [Na+], probably by a mechanism other than alteration in erythrocyte passive Na+ transport.

Animals↗
PubMed1988

Age-related effects of antihypertensive therapy with alpha-blockers.

Currently, the most important alpha-blockers used in treating hypertension are prazosin and its long-acting congeners, doxazosin and terazosin. Although there are minor age-related changes in the pharmacokinetics of these compounds, they result in no appreciable alteration in dose requirements. Overall, published evidence does not indicate any loss of responsiveness to alpha-blockade in the elderly. Despite the potential risks of first-dose hypotension and of postural hypotension, long-acting alpha-blockers may warrant further consideration as possible first-line therapy in elderly hypertensive patients. These agents allow the simplicity of once-daily dosing, and their cardiac and metabolic effects offer potential advantages.

Adrenergic alpha-Antagonists↗
PubMed1987

Erythrocyte cation fluxes during the menstrual cycle in normal female subjects.

1. Studies of erythrocyte cation transport mechanisms in vitro were performed on eight normotensive, premenopausal female subjects at the mid-points of the follicular and luteal phases of their menstrual cycles. Concurrent plasma concentrations of 17 beta-oestradiol, progesterone, aldosterone and renin activity were measured. 2. Ouabain-resistant, frusemide-resistant rubidium influx (an index of passive potassium diffusion) was significantly lower in the luteal than the follicular phase. 3. In further studies in four of the eight subjects, the mean rate constant of the rubidium influx measurement was also lower in the luteal than in the follicular phase. 4. There were no changes in Na+-K+ co-transport, sodium pump activity or intracellular cation concentrations throughout the cycle. 5. There was a tenfold fall in the mean plasma 17 beta-oestradiol/progesterone ratio, as well as increases in plasma aldosterone concentration and renin activity between the mid-follicular and mid-luteal phases. 6. We conclude that changes in plasma oestrogen/progesterone ratio during the menstrual cycle may be associated with alterations in passive potassium diffusion.

Adult↗
PubMed1987

Erythrocyte cation fluxes in the normotensive and hypertensive clients of a health screening clinic.

Erythrocyte cation transport was measured in vitro using 22Na+ and 86Rb+ uptake techniques in Caucasian men with newly-detected hypertension and in male control groups. The Na+, K+ cotransport [determined by ouabain-resistant frusemide-sensitive (ORFS) components of Na+ or Rb+ influx], sodium pump activity (determined by ouabain-sensitive Rb+ influx) and erythrocyte Na+ and K+ concentrations were not significantly altered in hypertensive men. The total Na+ influx in hypertensives (n = 59) was significantly greater (P less than 0.001) than in controls. The difference was mainly attributable to an increase in the ouabain-resistant frusemide-resistant component of this flux. The total Rb+ influx in hypertensives (n = 39) was also greater (P less than 0.005) than in controls. Overall, both total Na+ influx and total Rb+ influx were positively correlated (P less than 0.01) with diastolic blood pressure and with habitual dietary intake of alcohol. Multivariate analyses after controlling for the effect of blood pressure showed that mean corpuscular volume (MCV) and alcohol intake were statistically significant predictor variables for total Rb+ influx, although not for total Na+ influx. The results are compatible with increased diffusion of cations across the erythrocyte membrane in hypertension, but raise the question of a possible role of alcohol intake in mediating this effect.

Adult↗
PubMed1986

Ketanserin and prazosin: a comparison of antihypertensive and biochemical effects.

A randomized crossover trial was conducted in 15 patients with essential hypertension to compare the actions of prazosin, a specific alpha 1-adrenoceptor blocker, and ketanserin, an antagonist at alpha 1-adrenergic and serotonin receptors. After placebo dosing for 2 weeks, active drug was given double-blind in two 4-week phases. Satisfactory control of supine blood pressure was obtained in nine of the 12 subjects who completed the prazosin phase and 11 of the 15 subjects who completed the ketanserin phase. Whether comparison was based on supine, erect, postexercise, or ambulatory values, the blood pressure responses to prazosin (2 or 4 mg/day) and ketanserin (40 or 80 mg/day) were closely similar. Neither of the drugs significantly altered supine or erect pulse rates, body weight, serum triglyceride concentrations, plasma renin activity, or urinary aldosterone excretion, and their side effect profiles were similar. The serum cholesterol concentration was lowered by prazosin but was not affected by ketanserin. However, no other features were observed that distinguished the clinical effects of ketanserin from those of prazosin.

Adult↗
PubMed1986

Effects of dietary sodium deprivation on erythrocyte sodium concentration and cation transport in normotensive and untreated hypertensive subjects.

There is controversy about the effects of dietary sodium deprivation on cellular cation transport. Using washed erythrocytes for in vitro 22Na and 86Rb uptake studies, we studied the effects of a strict low-salt diet (20 mmol/day) for 4 days in 14 normotensive and 13 hypertensive subjects. Urinary sodium excretion fell from 147 +/- 13 to 18 +/- 3 mmol/24 h in the normotensive group and from 155 +/- 16 to 20 +/- 2 mmol/24 h in the hypertensive group. In both groups, there was a fall in plasma sodium concentration and activation of the renin-aldosterone axis. Both systolic and diastolic blood pressures fell in the hypertensive, but not the normotensive group. There were small but significant (P less than 0.025) decreases in cell cation concentrations and passive cation transport in the normotensive, but not the hypertensive group. No significant change in sodium pump activity or in Na+K+ cotransport was seen in either group. These observations provide no support for the concept that a decrease in dietary sodium intake can induce changes in cell cation transport, detectable in vitro, to which reduction in blood pressure may be attributed.

Adult↗
PubMed1986

Studies on the vasodilator actions of bucindolol in the rat.

Experiments were performed in anaesthetized rats to investigate the vasodilator actions of the beta-adrenoceptor antagonist bucindolol. Bucindolol (3 mg/kg) lowered blood pressure significantly in rats pretreated with (i) prazosin (0.4 mg/kg) (ii) prazosin (0.4 mg/kg) plus propranolol (0.5 mg/kg) or (iii) labetalol (0.5 mg/kg). Thus, a portion of the hypotensive effect of bucindolol was independent of effects on alpha- or beta-adrenoceptors. This was attributed to direct vasodilatation. In reserpinized anaesthetized rats bucindolol increased heart rate and thus had an intrinsic sympathomimetic action (ISA). The ISA was equipotent with that of isoprenaline at the 0.25 nmol/kg dose level, but declined with increasing bucindolol doses, probably due to the onset of beta-adrenoceptor blockade. An isolated perfused rat tail arteries constricted by perfusing with a high-K+ Krebs solution, bucindolol (10(-5) mol/l, 10(-4) mol/l) caused a significant reduction in perfusion pressure indicative of vasodilatation. Since the perfusate contained 10(-6) mol/l propranolol, the vasodilatation was not due to beta-adrenoceptor stimulation. These results are consistent with a direct vasodilator action of bucindolol. We suggest bucindolol lowers blood pressure by a complex mechanism involving beta-adrenoceptor blockade, alpha-adrenoceptor blockade, vasodilatation and perhaps beta 2-adrenoceptor stimulation.

Animals↗