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Biomedical subjects

G D Murray

Publications and source records attributed to G D Murray.

156 records · Page 9Linked to original sources
PubMed1984

Renal secretion of inactive renin and extraction of angiotensin II in renal artery stenosis in man: factors determining renal vein renin ratio.

Triplicate blood samples were obtained, without stimulation, simultaneously from the aorta and both renal veins in 24 untreated hypertensive patients with unilateral renal artery stenosis. Across the affected kidney the plasma concentrations of active renin, inactive renin and angiotensin II increased by 363% (P less than 0.001), 80% (P less than 0.05) and 100% (P less than 0.05) respectively. Thus the affected kidney was secreting both active and inactive renin, while appreciable quantities of angiotensin II were generated across the renal circulation on that side. Across the contralateral unaffected kidney there were no significant changes in concentration of active or inactive renin, indicating net suppression of secretion of both forms of renin. Plasma angiotensin II concentration was however markedly reduced, to 50% of the arterial value (P less than 0.001), in the contralateral renal vein, demonstrating renal extraction of angiotensin II. In 14 patients renal plasma flow was also measured. The ratio of active renin concentration between the two renal veins correlated more closely with the renal plasma flow to the affected kidney (r = -0.81; P less than 0.01) than with renin secretion rate on that side (r = +0.37; NS). Thus reduction in renal blood flow rather than increase in renin secretion appeared to be the major determinant of renal vein renin ratio.

Angiotensin II↗
PubMed1983

Enalapril in the treatment of hypertension with renal artery stenosis.

The converting enzyme inhibitor enalapril, in single daily doses of 10-40 mg, was given to 20 hypertensive patients with renal artery stenosis. The blood pressure fall six hours after the first dose of enalapril was significantly related to the pretreatment plasma concentrations of active renin and angiotensin II and to the concurrent fall in angiotensin II. Blood pressure fell further with continued treatment; the long term fall was not significantly related to pretreatment plasma renin or angiotensin II concentrations. At three months, 24 hours after the last dose of enalapril, blood pressure, plasma angiotensin II, and converting enzyme activity remained low and active renin and angiotensin I high; six hours after dosing, angiotensin II had, however, fallen further. The rise in active renin during long term treatment was proportionally greater than the rise in angiotensin I; this probably reflects the fall in renin substrate that occurs with converting enzyme inhibition. Enalapril alone caused reduction in exchangeable sodium, with distinct increases in serum potassium, creatinine, and urea. Enalapril was well tolerated and controlled hypertension effectively long term; only two of the 20 patients required concomitant diuretic treatment.

Adolescent↗
PubMed1983

Factors related to first dose hypotensive effect of captopril: prediction and treatment.

The blood pressure response to the first dose of captopril (6.25 mg, 12.5 mg, or 25 mg) was measured in 65 treated, severely hypertensive patients. Mean supine blood pressure was 187/108 mm Hg immediately before captopril was given. Twenty one patients experienced a fall in supine systolic pressure greater than 50 mm Hg, including five whose pressure fell more than 100 mm Hg and two whose pressure fell more than 150 mm Hg. Six patients developed symptoms of acute hypotension, including dizziness, stupor, dysphasia, and hemiparesis. Percentage reductions in blood pressure were greatest in those with secondary hypertension (p less than 0.05), high pretreatment blood pressure (p less than 0.05), and high concentrations of plasma renin and angiotensin II (p less than 0.01). No significant correlation was found between fall in blood pressure and serum sodium concentration, age, renal function, and the dose of captopril given. A severe first dose effect cannot be consistently predicted in individual patients who have received other antihypertensive drugs for severe hypertension. Such patients should have close medical supervision for at least three hours after the first dose of captopril.

Aged↗
PubMed1983

The effect of a 5-HT antagonist, ketanserin, on blood pressure, the renin-angiotensin system and sympathoadrenal function in normal man.

The role of endogenous 5-hydroxytryptamine (5-HT) in the control of blood pressure, the renin-angiotensin system and sympatho-adrenal function was investigated in normal man. Ketanserin (a specific 5-HT2 antagonist) administered intravenously caused a small decrease in blood pressure in salt-depleted recumbent subjects. A more marked postural fall in pressure occurred in both sodium-depleted and repleted normal subjects. Plasma active renin concentration and angiotensin II increased after administration of ketanserin, but plasma aldosterone, cortisol and noradrenaline were unchanged. 5-HT may be important in the control of blood pressure in man and specific 5-HT2 receptor antagonists could be a useful new class of antihypertensive agents.

Adrenal Glands↗
PubMed1983

Enalapril (MK421) in the treatment of hypertension with renal artery stenosis.

The converting enzyme inhibitor, enalapril, was given to 20 hypertensive patients with renal artery stenosis in a single daily dose of 10-40 mg. Enalapril effectively controlled hypertension long-term, and only two of the 20 patients required concomitant diuretic treatment. The blood pressure reduction 6 h after the first dose of enalapril was significantly related to pre-treatment plasma concentrations of active renin and angiotensin II (AII), and to the concurrent fall in AII. Blood pressure fell further with continued treatment; the long-term reduction was not significantly related to pretreatment plasma renin or angiotensin II. At three months, 24 h after the last dose of enalapril, blood pressure, plasma AII and converting enzyme activity remained low, and active renin and angiotensin I (AI) high; 6 h after dosing, AII had, however, fallen further. During prolonged therapy, the increase of active renin was proportionately greater than that of angiotensin I. Enalapril alone caused a long-term reduction in exchangeable sodium, with slight increases in serum potassium, creatinine and urea. Enalapril alone did not impair overall renal function in five patients with bilateral renal lesions despite effective blood pressure reduction. Enalapril was well tolerated with no serious side-effects. Enalapril given once daily is effective in controlling hypertension associated with renal artery stenosis.

Adolescent↗
PubMed1983

Angiotensin II receptors in resistance vessels.

We have studied binding of 125I-angiotensin II (AII) to a membrane fraction prepared from mesenteric arterial arcades of the rat. Two problems were encountered: heterogeneity of binding sites and appreciable degradation of tracer that could not be inhibited without adversely affecting binding capacity. Analysis of binding results was carried out using a non-linear regression method allowing correction for tracer and receptor degradation and direct estimation of binding constants. From saturation and dissociation curves it was apparent that there were two classes of binding sites. KD of the high affinity site was within the physiological range of plasma AII concentration at between 0.05 and 0.5 nM. Calcium, magnesium and manganese increased binding capacity, whereas EDTA and EGTA had the opposite effect. Potassium increased binding capacity but had a biphasic effect in the presence of sodium.

Angiotensin II↗
PubMed1982

Converting-enzyme inhibitor enalapril (MK421) in treatment of hypertension with renal artery stenosis.

Enalapril maleate (MK421), a new inhibitor of angiotensin converting enzyme, in single daily doses of 1.25-40 mg was assessed in five patients with hypertension and renal artery stenosis. Only small falls in plasma angiotensin II concentrations were seen at doses less than 10 mg; even with 10 and 20 mg, angiotensin II concentrations had risen again 24 hours from the last dose. During long-term treatment with 10-40 mg daily all patients achieved good blood-pressure control. No significant changes of body sodium or potassium values were seen. The drug was well tolerated with no serious side effects. These findings are evidence of the efficacy and acceptability of enalapril in the medical management of hypertension with renal artery stenosis.

Adult↗
PubMed1981

The effect of oral prazosin on blood pressure and plasma concentrations of renin and angiotensin II in man.

1. We studied the effect of oral prazosin on blood pressure, plasma active renin and angiotensin II in 16 recumbent hypertensive patients between 09.00 and 12.00 hours. 2. In untreated patients there were no significant changes in blood pressure, plasma active renin or angiotensin II during the 3 h period. 3. After an initial dose of prazosin (2 mg) there was a significant fall in recumbent blood pressure with progressive increases in plasma active renin and angiotensin II concentrations. 4. After 3--4 weeks' treatment with oral prazosin only, recumbent blood pressure at 09.00 hours, 15 h after the last dose of prazosin, was significantly lower than before treatment, but plasma active renin and angiotensin II were not significantly different from untreated values. 5. After the usual morning dose of prazosin, blood pressure did not change, but there were significant rises in plasma active renin and angiotensin II, less marked than after the first dose of prazosin. 6. Prazosin therefore stimulates the renin--angiotensin system acutely, both after the initial dose and during long-term therapy; however, no effect on renin and angiotensin II is apparent 15 h after the last dose of prazosin.

Administration, Oral↗
PubMedDate not supplied

Assessing the performance and clinical impact of a computerized prognostic system in severe head injury.

The ability to predict outcome in the early stages of severe head injury would have several uses. A computerized system which has been developed in Glasgow to assist clinicians in this task, based on information from over 2500 severely head-injured patients, is described, with particular attention to the testing of the statistical properties of the system, and, more importantly, the assessment of its clinical impact.

Craniocerebral Trauma↗
PubMedDate not supplied

Similarity of idiopathic aldosteronism and essential hypertension. A statistical comparison.

There is clinical, biochemical, and pathological evidence that idiopathic aldosteronism is part of a continuum which includes low-renin and normal-renin essential hypertension. In a retrospective statistical study, 89 patients with essential hypertension have been compared with 22 cases of idiopathic aldosteronism and 34 cases of aldosterone-secreting adrenal adenomas. Measurements of serum sodium, potassium, bicarbonate, and plasma angiotensin II concentrations and estimates of exchangeable sodium and potassium were obtained for individual patients. By using various combinations of these biochemical variables, a statistic, the Mahalanobis distance, was described for each of the three populations, essential hypertension, idiopathic aldosteronism, and adrenal adenomas. For each combination of variables, the distribution of the idiopathic aldosteronism group resembled that of the essential hypertension group more closely than that of the aldosterone-secreting adrenal adenoma group. Thus, the use of this statistical technique provides further evidence of the similarity of essential hypertension and idiopathic aldosteronism.

Adenoma↗
PubMedDate not supplied

Assessing the clinical impact of a predictive system in severe head injury.

Many computer-assisted diagnostic or prognostic systems have been described in the literature, but as yet such systems have had little impact upon routine clinical practice. There are many possible explanations for the limited success which these systems have enjoyed, but one of the most significant must be the dearth of well-designed and carefully executed trials to assess their performance. Many evaluations only address the scientific question of whether the diagnoses or prognoses are accurate; they stop short of answering the crucial pragmatic question of whether the system benefits patients, i.e. is clinical care improved by the use of such a system? This brief paper describes a predictive system in severe head injury which has been developed by an international group based in the Institute of Neurological Sciences at the Southern General Hospital, Glasgow. The various steps involved were first the establishment of a clinical databank according to a strict protocol and with carefully designed scales to quantify the impairment of consciousness and outcome, the development of prognostic models relating outcome to initial severity, the comparison of the performance of this model with predictions made by clinicians, and finally a multi-centre prospective trial assessing the clinical impact of the system. The results of this trial are not yet available, but a consideration of the design of the trial raises important points which are relevant to many other clinical fields where 'decision aids' need to be evaluated.

Craniocerebral Trauma↗