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G S Stokes

Publications and source records attributed to G S Stokes.

At least 55 records · Page 3Linked to original sources
PubMed1986

Measurement of circulating sodium-pump inhibitory activity in uraemia and essential hypertension.

By measuring in vitro the effect of deproteinized plasma on canine kidney Na+K+-ATPase activity, evidence was sought for the presence of a circulating inhibitor of the enzyme in 31 patients with end-stage renal failure, 10 patients treated with digoxin, and 22 patients with untreated essential hypertension. In the renal failure group, mean Na+K+-ATPase activity with plasma samples taken just before a regular haemodialysis was 88% of that obtained with plasma from a normotensive control group (P less than 0.001). In digoxin-treated patients, the result was 94% of that obtained in control subjects (P less than 0.005). There was no significant difference in mean Na+K+-ATPase activity with plasma, between the hypertensive and control groups, or between age- and sex-matched subsets of these groups. The hypertensive group did not differ significantly from the control group in plasma renin activity or erythrocyte Na+ concentration. It was concluded that a circulating digitalis-like sodium-pump inhibitor was readily detectable in volume-expanded renal failure, but not in normal-renin essential hypertension.

Adult↗
PubMed1986

Studies that question the existence of alpha-2 adrenoceptors in tail arteries of normotensive Sprague-Dawley rats.

Many pharmacological studies have demonstrated two distinct types of alpha adrenoceptor in the vasculature; these receptors have been named alpha-1 and alpha-2. In the present study, using isolated perfused tail arteries from normotensive Sprague-Dawley rats, we have demonstrated two types of alpha adrenoceptor but neither of these could be classified as an alpha-2 adrenoceptor. Dose-dependent contraction of rat tail arteries was produced by the following alpha adrenoceptor agonists or agonist-antagonist combination: phenylephrine (PE alpha-1), clonidine (alpha-1 and alpha-2), clonidine in the presence of 10(-7) M prazosin (alpha-2) and BHT-920 (alpha-2). The ED50 values for PE and clonidine were four orders of magnitude lower than those for clonidine plus prazosin and BHT-920. In addition, the action of PE was faster in onset than that of BHT-920, reached a higher maximum (5-fold) and attenuated more rapidly than that of BHT-920. The specific alpha-2 adrenoceptor antagonist yohimbine, in concentrations as high as 10(-6) M, did not antagonize arterial responses to BHT-920. However, responses to BHT-920 were antagonized by the alpha-1 adrenoceptor antagonist prazosin, in concentrations as low as 10(-10) M, and by the serotonin/alpha-1 adrenoceptor antagonist ketanserin (10(-7) M). These results suggest that the two alpha-adrenoceptor types in isolated rat tail arteries are both of the alpha-1 type. We also found that whereas responses to PE were stable and reproducible between 2 and 5 hr of arterial perfusion, responses to BHT-920 increased progressively over 5 hr. The latter effect probably resulted from a gradual disappearance of the arterial endothelium.

Animals↗
PubMed1985

Bucindolol has serotonin and alpha-adrenoceptor blocking properties.

Bucindolol is a new beta-adrenoceptor antagonist that lowers blood pressure partly via direct vasodilation. We have investigated the mechanism of the antihypertensive action of bucindolol using the isolated perfused rat tail artery preparation. Bucindolol caused a parallel shift to the right of the dose-response curves for both serotonin (5-HT) and phenylephrine (PE), indicating competitive antagonism. The pA2 values were 5.9 +/- 0.2 (5-HT) and 7.18 +/- 0.10 (PE). The calculated potency ratio (PE:5-HT) was 19. Thus, bucindolol was found to have weak serotonin antagonist as well as alpha-adrenergic antagonist properties in addition to its documented beta-adrenoceptor antagonist properties. This appears to be a novel combination of antagonist properties. Bucindolol also reduced the maximal response to 5-HT but had no effect on the maximal response to PE. In these respects, bucindolol acts similarly to prazosin (alpha-adrenoceptor blocker) and ketanserin (5-HT antagonist and alpha-adrenoceptor blocker). These results are consistent with our proposal that 5-HT receptors and alpha-adrenoceptors overlap on the cell surface, sharing common binding sites, such that alpha-adrenoceptor blockade causes interference with the full expression of 5-HT receptor stimulation.

Adrenergic alpha-Antagonists↗
PubMed1985

Erythrocyte cation transport is sex-related and is modified by oral contraceptives.

Cation transport across the erythrocyte membrane was studied in normotensive male and female subjects, 20 to 45 years of age. Inward sodium-potassium cotransport was found to be significantly greater in men than in women who were not taking oral contraceptives. Intracellular potassium concentration was lower in men than in women, and was inversely correlated with cotransport. Women who were using oestrogen-progestogen oral contraceptives had higher cotransport than those who were not. It is concluded that a difference in cotransport exists between Caucasian men and women, which is not evident if women are taking oral contraceptives, and which could invalidate comparisons of cation transport between subject groups that are not sex-matched.

Adult↗
PubMed1985

Essential hypernatremia: disordered thirst and blood pressure control.

A 24 year old man developed partial central diabetes insipidus with impaired thirst and an elevated osmotic threshold to the release of arginine vasopressin (AVP). Plasma AVP was present in inappropriately small concentrations despite severe hyperosmolality. In addition, marked hypertension accompanied this disorder and all abnormalities, including the hypertension, responded to 1-desamino-8-D-arginine vasopressin therapy. Several lines of evidence suggest this disorder may be a disturbance of hypothalamic function.

Adult↗
PubMed1985

Altered erythrocyte cation transport related to hypertension or oral contraception.

Intracellular cation concentrations (Nai, Ki), and the influx of Rb86 and of Na22 were measured in the erythrocytes of 22 normal women with no family history of hypertension, 16 women with untreated essential hypertension, and 14 normotensive women treated with hormonal contraceptives. Values for total Rb influx, and for its components denoting sodium pump activity (ouabain-sensitive) and Na, K co-transport (ouabain-resistant, frusemide-sensitive), were significantly greater in the hypertensive and contraceptive-treated groups than in the normal group. Na, K cotransport measured by Na influx (frusemide-sensitive) was found to be significantly increased in the contraceptive-treated but not the hypertensive group. Passive sodium diffusion (frusemide-resistant Na influx) and Ki did not differ significantly between groups. Nai was lower in the hypertensive group than in the other two groups. These findings support the hypothesis that hypertension or hormonal contraception are associated with increased leakage of K ions from erythrocytes, without a corresponding increase in passive Na influx: the change in cell membrane permeability is compensated for by increases in Na, K co-transport and sodium pump activity, adjusted to allow for altered differential permeability to K and Na ions.

Adult↗
PubMed1984

Surgical management of primary aldosteronism (Conn's syndrome), a correctable cause of hypertension.

Clinical, operative and pathological findings in a series of 18 patients with aldosterone producing adrenal cortical adenomas are reviewed. All patients presented with hypertension and hypokalaemia. The main challenges in preoperative diagnosis were to differentiate primary aldosteronism from other causes of hypokalaemia, such as diuretic therapy, to establish the presence of a discrete adenoma and to localize the tumour to the left or right adrenal gland. A high rate of success was achieved in predicting a surgical diagnosis of aldosterone-producing adenoma. This was attributed to thorough biochemical evaluation of the underlying metabolic state by measurement of renal potassium handling and by determining the responses of the renin-aldosterone axis to changes in sodium balance. Preoperative tumour localization, using adrenal phlebography or scintiscanning, was accomplished in only eight cases. Our experience suggests that the transabdominal approach is preferable for cases in which a unilateral lesion is not clearly identified by imaging techniques.

Adenoma↗
PubMed1984

Use of an intravenous sodium load in screening for primary hyperaldosteronism.

A sodium loading test was performed in 35 patients presenting with hypertension and hypokalemia. In 14 of these patients, intravenous administration of 0.9% saline (2 l in 4 h) on two consecutive days caused urinary aldosterone excretion to fall to values within the range for normal volunteers. The other 21 patients, in whom urinary aldosterone excretion did not decline following two days of saline loading, or in whom pronounced hypokalemia after the first day of loading precluded further saline infusion, were designated as having primary aldosteronism. Seventeen of this group underwent surgery and discrete adrenal adenomas were found in 16. When serum potassium concentration, plasma renin activity or the relationships of serum potassium to concurrent urinary potassium excretion or of urinary aldosterone excretion to plasma renin activity were used as alternative diagnostic criteria for primary aldosteronism, overlapping of the two groups occurred. It is concluded that measurement of urinary aldosterone excretion after intravenous sodium loading is a useful test in the test in the identification of primary aldosteronism due to aldosterone-producing adenoma. In this series the saline loading test was more specific in diagnosis than criteria based on serum and urinary potassium, plasma renin activity or unsuppressed aldosterone excretion.

Adrenal Cortex Neoplasms↗
PubMed1984

Review of the use of alpha-adrenoceptor antagonists in hypertension.

The discovery of alpha-adrenoceptor antagonists with selectivity for the post-synaptic alpha 1-adrenoceptor has yielded a group of antihypertensive agents of high specificity in blocking sympathetic impulses to resistance and capacitance vessels. This group differs from the previously-developed alpha-adrenoceptor blockers, phentolamine and phenoxybenzamine, in that they do not block the pre-synaptic alpha 2-adrenoceptors which modulate the release of neurotransmitter, and therefore do not cause as much reflex activation of the sympathetic nervous system. These differences have important clinical implications in regard to the antihypertensive efficacy of prazosin and its congeners, and to their use in combination with beta-blockers. Evidence that there are structural similarities between alpha-adrenoceptors and serotonin receptors is supported by the finding that ketanserin, developed for its 5HT2-receptor blocking property, exerts at least part of its antihypertensive action through alpha 1-adrenoceptor blockade. The most important limiting factor in the clinical application of prazosin is the postural hypotension and tachycardia associated with initial dosing. It is of some academic interest that these first-dose effects may be utilized to predict the long-term efficacy of the drug in individual patients. From a practical viewpoint, they may be largely avoided by starting therapy with small doses and recognising factors, such as a contracted plasma volume, which can sensitize the patient to sudden withdrawal of sympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1983

On the combination of alpha- and beta-adrenoceptor blockade in hypertension.

A randomized double-blind crossover trial was conducted in 20 patients with moderate to severe hypertension to compare the efficacy of labetalol, which combines alpha- and beta-adrenoceptor blocking properties, with that of metoprolol alone or in combination with prazosin. After placebo for 1 wk, active medication was given in two 6-wk phases. During one phase, metoprolol (100 to 400 mg/day) was given with prazosin (2 to 4 mg/day) as an option in the last 3 wk, whereas during the other phase, labetalol (200 to 1000 mg/day) was given alone. Satisfactory control of supine blood pressure was obtained in 10 patients with metoprolol and in another four patients after the addition of prazosin. During the labetalol phase, blood pressure control was achieved in 11 of 19 patients tested. Gastrointestinal disturbances, nasal congestion, impotence, failure to ejaculate, scalp tingling, and headache were more prevalent in the labetalol phase than in the other. In four cases these occurred in patients who did not require prazosin. Supine, erect, and exercise pulse rates were reduced by both metoprolol with or without prazosin and by labetalol; the effects were less in the labetalol phase. These differences could arise from an action of labetalol on cardiac presynaptic alpha-adrenoceptors. Adjunctive use of prazosin in nonresponders to metoprolol increases the response rate and avoids unnecessary deployment of alpha-adrenoceptor blockade in patients whose blood pressure can be controlled by beta-blockade alone.

Adult↗
PubMed1983

The renin angiotensin system--its physiology and role in disease states.

The renin-angiotensin system is one of a number of interlinked mechanisms regulating vascular resistance and blood volume. Under certain conditions it may become a predominant factor in maintaining vascular tone. Knowledge about these conditions (sodium depletion, mineralocorticoid deficiency, renovascular hypertension and iatrogenic hyperreninaemic states) is important for the safe and effective use of drugs which inhibit the renin-angiotensin system. Measurements of plasma renin activity are useful in the diagnostic assessment of hypertensive patients with hypokalaemia or evidence of renal artery stenosis. They may also have a place in the management of refractory or dialysis-resistant hypertension. Their use in the selection of antihypertensive therapy for the individual patient is controversial. Sequential measurements of plasma renin are helpful in analysing states of electrolyte depletion, and in titrating therapy for Addison's disease.

Aldosterone↗
PubMed1982

Alcohol consumption and blood pressure: survey of the relationship at a health-screening clinic.

We studied the association between stated alcohol consumption and blood pressure, making allowance for age, adiposity and smoking in 13535 men and 7385 women who were not receiving antihypertensive treatment. They represented a wide cross-section of the inner Sydney working population with 95% aged between 18 and 70. We found a high degree of linear correlation between stated alcohol consumption and blood pressure, diastolic and systolic. This relationship was independent of age, adiposity and smoking. For each 100 g/week increase in stated alcohol consumption, diastolic blood pressure increased by 0.12 kPa (0.92 mmHg) in men and by 0.20 kPa (1.5 mmHg) in women; no threshold for this effect was evident. A plateau appeared at about 500 g/week. Blood pressure increased significantly with age and adiposity (Quetelet's index). Smoking was associated with a lower diastolic blood pressure. The difference in mean diastolic blood pressure between smokers and non-smokers was 0.20 kPa (1.5 mmHg) for men and 0.27 kPa (2.1 mmHg) for women.

Adolescent↗
PubMed1982

Combined use of prazosin and beta-blockers in hypertension.

Combined use of prazosin and beta-blockers in a hypertension clinic over a 3-year period was surveyed by means of a computerized record system. Of the 1,250 patients in the clinic, 171 (14%) had been treated with this combination for periods averaging 17 months. Prazosin was administered with a beta 1-selective beta-blocker in 94 cases and with a beta 1 + beta 2-blocker in 100 cases; 23 patients had received treatment with both combinations. Diuretics were given in 86% of cases and other antihypertensive drugs in 19%. The population treated had a high incidence of severe hypertension, with initial diastolic pressure greater than 120 mm Hg in 38% and between 100 and 120 mm Hg in 50%. The percentage of patients with diastolic pressure less than 100 mm Hg was 12% initially and 79% at the end of the treatment period. Side effects necessitated withdrawal of therapy in 35 cases. These were referable in 19 cases to prazosin and in 16 to beta-blockers. Prazosin was found to be more effective in lowering blood pressure in combination with beta 1-blockers than with beta 1 + beta 2-blockers, although there were fewer severe side effects with beta 1-blockers.

Adrenergic beta-Antagonists↗
PubMed1981

Studies in the rat on bucindolol, a new antihypertensive agent with beta-adrenoceptor blocking properties.

The properties of a new antihypertensive agent, bucindolol, were studied in the anaesthetized rat. When administered intravenously in the dose range 0.03 to 1.0 mg/kg, bucindolol evoked dose-related decreases in mean arterial blood pressure wtih relatively little change in heart rate. Bucindolol retained nearly 50% of its hypotensive activity after ganglionic blockage with pentolinium. When administered intravenously in a dose of 0.25 mg/kg, bucindolol caused approximately 1000-fold and 100-fold shifts to the right in the dose-response curves for isoprenaline-induced chronotropic activity and hypotensive activity, respectively. The same dose of bucindolol caused a decrease in pressor responsivity to angiotensin II, no significant change in that to noradrenaline, and an increase in that to adrenaline. Bucindolol was an effective hypotensive agent, which under the conditions of test, had relatively little effect on basal heart rate, exhibited no significant alpha-adrenoceptor blocking activity in the dose range tested, had potent beta-adrenoceptor blocking properties, and exhibited an apparent direct relaxant effect on vascular smooth muscle.

Adrenergic beta-Antagonists↗