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Biomedical subjects

L M Wing

Publications and source records attributed to L M Wing.

89 records · Page 5Linked to original sources
PubMed1977

Clonidine withdrawal in hypertension. Changes in blood-pressure and plasma and urinary noradrenaline.

Treatment was interrupted abruptly in 6 hypertensive patients receiving clonidine 0-45-5-4 mg daily. Blood-pressure rose to pretreatment levels within 24-48 h of withdrawal and was accompanied by insomnia, headache, flushing, sweating, and apprehension. These symptoms began 18-20 h after the last dose of clonidine. Plasma-noradrenaline levels and urinary catecholamine excretion increased 24-72 h after withdrawal of clonidine. The subjective symptoms were most prominent in patients on higher doses (greater than 1 mg/day) and in those who had previously been receiving treatment with other antihypertensive drugs. One patient on a very low daily dose (0-15 mg) of clonidine had no symptoms and no significant changes in blood-pressure or catecholamine production after drug withdrawal.

Adult↗
PubMed1977

Apparent resistance to hypotensive effect of clonidine.

Clonidine failed to reduce the blood pressures of two patients with essential hypertension. On was given 5-4 mg/day and the other 6 mg/day, and their respective peak plasma clonidine concentrations were 26-2 ng/ml and 14-4 ng/ml. Several months after the end of clonidine treatment a single oral dose of 0-3 mg of clonidine produced maximum falls in blood pressure of 30/22 mm Hg and 88/41 mm Hg with peak plasma clonidine concentrations of 1-4 ng/ml and 0-9 ng/ml. Resistance to the hypotensive effect of high doses of clonidine may be due to stimulation of peripheral alpha-adrenoceptors causing vasoconstriction, which maintains a raised blood pressure.

Adult↗
PubMed1977

The central hypotensive effect of clonidine. Studies in tetraplegic subjects.

A single oral dose of 300 microng of clonidine lowered systolic blood pressure by 20 +/- 4 mm Hg and diastolic blood pressure by 13 +/- 4 mm Hg in five healthy normotensive subjects (controls). Heart rate fell from 56 +/- 2 to 52 +/- 2 beats/min. In six tetraplegic subjects with physiologically complete chronic cervical spinal cord transection above the level of the sympathetic outflow, the same dose of clonidine did not significantly lower either systolic or diastolic blood pressure. Heart rate fell from 67 +/- 4 to 53 +/- 2 beats/min. Peak plasma concentrations of clonidine, measured by mass fragmentography, and elimination of the drug from plasma were similar in tetraplegic and control subjects and there was no difference in the incidence of the principal side effects of clonidine--sedation and dry mouth. Although the number of subjects studied is small, the absence of a fall in blood pressure after clonidine in the tetraplegic subjects suggests that the hypotensive action of clonidine in man is dependent on intact descending bulbospinal pathways and is mediated by withdrawal of sympathetic tone and provides direct evidence that some antihypertensive drugs may lower blood pressure in man by a direct action on the brain.

Adult↗
PubMed1977

Effects of clonidine on biochemical indices of sympathetic function and plasma renin activity in normotensive man.

1. A single oral dose of clonidine hydrochloride (300 microgram) lowered systolic blood pressure by 20+/-2 mmHg and diastolic blood pressure by 15+/-2 mmHg in seven healthy normotensive subjects. 2. Resting supine plasma noradrenaline concentration fell from 2-42+/-0-47 nmol/l before dosing to a minimum of 0-59+/-0-18 nmol/l at 6 h. The value subsequently rose and was not significantly different from that before the dose at 12 h. There was a significant reduction in urinary free catecholamine excretion in the first 12 h after dosing. 3. Resting supine plasma renin activity before dosing was 0-95+/-0-16 pmol of angiotensin I h-1 ml-1 of plasma and rose significantly after clonidine to 3-50+/-0-39 pmol of angiotensin I h-1 ml-1 of plasma at 6 h. By 12 h plasma renin activity had returned to control values. 4. When the same subjects were studied on a control, drug-free, day under the same conditions, there was no significant change in blood pressure or plasma noradrenaline. Although plasma renin activity rose during this control day, it was significantly lower than after clonidine. 5. In normotensive subjects single doses of clonidine lower blood pressure and are associated with a reduction of sympathetic nervous activity. Delayed elevation of plasma renin activity may be secondary to the fall in blood pressure. There is no evidence for an overshoot of sympathetic activity after a single dose of clonidine.

Adult↗
PubMed1977

Mechanism of cardiovascular effects of clonidine in conscious and anesthetized rabbits.

The actions of intravenous clonidine [2-(2,6 dichlorophenylamino)-2-imidazoline hydrochloride] on blood pressure and heart rate were examined in conscious rabbits. Complete transection of thecervical spinal cord increased the intensity and duration of the hypertensive effect of 30 microgram/kg of clonidine and completely abolished the fall in blood pressure. Heart rate slowing by clonidine was reduced. Result were similar 1 hour, 24 hours and 7 days after cord transection. Bilateral aortic sinus nerve section (baroreceptor deafferentation) increased both the hypertensive and hypotensive action of clonidine but reduced the bradycardia. When cervical cord transection was combined with batensive action, were abolished. We conclude that whereas the hypertensive action results from a direct effect on peripheral adrenoceptors, the fall in blood pressure is related to a reduction in sympathetic tone mediated at the level of the brain stem or more rostrally. The heart rate slowing results from both a reduction in sympathetic tone and also an enhanced vagal outflow. The increase in vagal tone seems to be dependent on the intergrity of baroreceptor afferent pathways.

Animals↗
PubMed1976

Double-blind factorial trial of prindolol and hydrochlorothiazide in hypertension.

The antihypertensive actions of the beta-adrenergic blocking agent, prindolol, and of the diuretic, hydrochlorothiazide, were analysed in a double-blind randomized 2 X 2 factorial trial in 16 patients. There were four eight-week phases in which patients received prindolol alone, hydrochlorothiazide alone, prindolol plus hydrochlorothiazide in combination, and no treatment. Both drugs were given in fixed doses: prindolol, 10 mg three times per day; hydrochlorothiazide, 50 mg per day. Blood pressure was measured weekly, alternately at the outpatient clinic and at home. Supine mean arterial pressure (MAP) in resting patients fell from 127 mm Hg in the placebo phase to 117 mm Hg with hydrochlorothiazide alone, 116 mm Hg with prindolol alone, and 111 mm Hg with the combination of prindolol and hydrochlorothiazide. (The standard error of difference between treatments was +/-3-58). A mean factorial effect of -7 mm Hg for hydrochlorothiazide (P less than 0-01) and -8 mm Hg for prindolol (P less than 0-01) was obtained, and the two drugs acted in an additive manner. The effects on standing blood pressure in resting patients were similar. No serious side effects were noted.

Adult↗
PubMed1976

Pharmacokinetic and pharmacological studies with clonidine in normal subjects.

1. A highly specific and sensitive assay based on stable isotope dilution and mass fragmentography has been developed to measure clonidine in plasma. 2. Plasma half-lives of clonidine ranged from 6-9 to 9-4 h in five normotensive subjects. 3. Plasma clonidine concentration correlated with reduction in salivary flow and degree of sedation but not with change in blood pressure.

Adult↗
PubMed1975

Central serotonergic neurons and experimental neurogenic and renal hypertension in the rabbit.

1. Rabbits received intracisternal injections of 5,6-dihydroxytryptamine (5,6-DHT) in order to ablate central serotonergic nerves and deplete central serotonin stores. Depletion was most marked in the spinal cord where serotonin concentration was reduced to less than 50% of that in rabbits given control injections. 2. In normal rabbits, intracisternal 5,6-DHT caused a transient reduction in arterial pressure, which was maximal 1 week after injection. 3. Intracisternal 5,6-DHT completely prevented the neurogenic hypertension produced by sinoaortic denervation in control animals and reversed it when given after sustained neurogenic hypertension had developed in denervated animals. These studies suggest that central serotonergic neurons participate in the baroreceptor reflex arc. 4. Intracisternal 5,6-DHT did not modify the renal hypertension that follows bilateral renal wrapping.

5,6-Dihydroxytryptamine↗
PubMedDate not supplied

The effects of indomethacin in treated hypertensive patients.

1. Twelve treated hypertensive patients (ages 58-71 years) who had also been treated for joint disease participated in a randomized double-blind crossover placebo-controlled study to investigate the effects of indomethacin (25 mg three times daily) on blood pressure and biochemical parameters over a 6-week period. 2. Blood pressure was increased in all patients throughout the indomethacin treatment period (P less than 0.001)--average mean blood pressure increases were 9 mmHg (casual), 8 mmHg (supine), 10 mmHg (standing). 3. The blood pressure increase during indomethacin treatment was independent of the particular antihypertensive regimen in use. 4. Plasma aldosterone concentration was reduced by 50% (P less than 0.01), plasma renin activity was reduced by 43% (P = 0.102) and plasma urea concentration was increased by 17% (P less than 0.001) during indomethacin treatment. 5. The findings confirm that indomethacin impairs the blood pressure lowering effect of antihypertensive regimens.

Aged↗
PubMedDate not supplied

Second Australian National Blood Pressure Study (ANBP2). Australian Comparative Outcome Trial of ACE inhibitor- and diuretic-based treatment of hypertension in the elderly. Management Committee on behalf of the High Blood Pressure Research Council of Australia.

The Second Australian National Blood Pressure Study (ANBP2) is a comparative outcome trial being conducted in general practices throughout Australia of ACE inhibitor- and diuretic-based treatment in 6000 hypertensive patients aged 65-84 years. The study is using a prospective randomised open-label design with blinding of endpoint assessments. The primary objective is to determine whether there is any difference in total cardiovascular events (fatal and non-fatal) over a five year treatment period between the two treatment regimens. Eligible hypertensive patients (average sitting blood pressure at the 2nd and 3rd screening visits > 160 mm Hg systolic and/or > 90 mm Hg diastolic) may be either untreated or previously treated and should have no history of recent cardiovascular morbidity or serious intercurrent illness. Patients are randomised to one of the treatment arms with randomisation stratified for practice and for age. Following randomisation each patient's blood pressure is managed by his/her general practitioner according to guidelines relevant to each treatment arm. Over 700 patients have now been randomised with recruitment intended to be complete by the end of 1997.

Aged↗
PubMedDate not supplied

Influence of cimetidine, sulfinpyrazone, and cigarette smoking on theobromine metabolism in man.

Theobromine metabolism and clearance were investigated at steady-state under chronic oral dosing conditions in eight healthy volunteers, four of whom were cigarette smokers. The subjects were studied before and after separate 1 week pretreatments with cimetidine (1 g/day) and sulfinpyrazone (800 mg/day). Theobromine plasma clearance (ClTB) was 33% higher in smokers than in non-smokers due to induction of all metabolic pathways (3-demethylation, 7-demethylation, and formation of 6-amino-5-(N-methylformylamino)-1-methyluracil (AMMU]. 7-Demethylation was induced by cigarette smoking to a greater extent than the other pathways. Cimetidine pretreatment inhibited theobromine 3-demethylation and AMMU formation resulting in a 27% decrease in ClTB in the combined smoker/nonsmoker group. The 7-demethylation pathway was unaffected by cimetidine. In contrast, sulfinpyrazone pretreatment increased ClTB by 50% in the whole group by approximately equal induction of each metabolic pathway. The extent of induction due to sulfinpyrazone was 2.4-fold greater in nonsmokers than in smokers. When compared with previous data relating to theophylline, the results suggest that theobromine 3-demethylation is mediated by the same form(s) of cytochrome P-450 involved in theophylline demethylation, while a second form(s) of cytochrome P-450 is involved in theobromine 7-demethylation and theophylline 8-hydroxylation. In addition, since AMMU formation was inhibited by cimetidine and induced by cigarette smoking and sulfinpyrazone, it would appear that the conversion of theobromine to AMMU is also mediated by cytochrome P-450.

Adult↗
PubMedDate not supplied

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