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Biomedical subjects

J McMurray

Publications and source records attributed to J McMurray.

At least 109 records · Page 6Linked to original sources
PubMed1990

Free radical scavenging: a potentially beneficial action of thiol-containing angiotensin converting enzyme inhibitors.

Free radical (FR) scavenging may be a therapeutically useful adjunctive property of angiotensin converting enzyme (ACE) inhibitors. In this study we have shown that SH-containing ACE inhibitors (captopril, epicaptopril, zofenopril) are potent FR scavengers at a concentration of 4 x 10(-5) M whereas non-SH ACE inhibitors (enalaprilat, quinaprilat and perindoprilat) have no FR-scavenging activity at this concentration. Furthermore, the SH-containing agents preferentially scavenged general radicals rather than superoxide radicals, i.e. suggesting that these drugs would be effective in quenching the culprit FR in ischaemia/reperfusion injury.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Novel exercise protocol suitable for use on a treadmill or a bicycle ergometer.

Many exercise protocols are in use in clinical cardiology, but no single test is applicable to the wide range of patients' exercise capacity. A new protocol was devised that starts at a low workload and increases by 15% of the previous workload every minute. This is the first protocol to be based on exponential rather than linear increments in workload. The new protocol (standardised exponential exercise protocol, STEEP) is suitable for use on either a treadmill or a bicycle ergometer. This protocol was compared with standard protocols in 30 healthy male volunteers, each of whom performed four exercise tests: the STEEP treadmill and bicycle protocols, a modified Bruce treadmill protocol, and a 20 W/min bicycle protocol. During the two STEEP tests the subjects' oxygen consumption rose gradually and exponentially and there was close agreement between the bicycle and the treadmill protocols. A higher proportion of subjects completed the treadmill than the bicycle protocol. Submaximal heart rates were slightly higher during the bicycle test. The STEEP protocol took less time than the modified Bruce treadmill protocol, which tended to produce plateaux in oxygen consumption during the early stages. The 20 W/min bicycle protocol does not take account of subjects' body weight and consequently produced large intersubject variability in oxygen consumption. The STEEP protocol can be used on either a treadmill or a bicycle ergometer and it should be suitable for a wide range of patients.

Adult↗
PubMed1989

Effects of atenolol, verapamil, and xamoterol on heart rate and exercise tolerance in digitalised patients with chronic atrial fibrillation.

The aim of the study was to compare the effects of atenolol (50 mg b.i.d.), verapamil (80 mg b.i.d.), xamoterol (200 mg b.i.d.), and matching placebo on heart rate (HR) and exercise tolerance in digitalised patients with chronic atrial fibrillation. Each treatment was taken for 4 weeks, and digoxin was continued throughout the study. During treatment with placebo (digoxin alone), the mean postexercise heart rate was 164 beats/min, and four subjects had rates of greater than or equal to 170 beats/min. Atenolol, verapamil, and xamoterol achieved significantly better control of exercise-induced tachycardia, mean postexercise heart rates being reduced to 120, 131, and 130 beats/min, respectively (p less than 0.01 for each). However, minimum HRs less than or equal to 45 beats/min occurred during treatment with placebo, atenolol, and verapamil, whereas treatment with xamoterol was associated with a minimum heart rate of 56 beats/min. Treatment with atenolol was associated with a marked reduction in maximum treadmill walking distance (mean 356 m) as compared both with placebo (mean 421 m, p less than 0.01) and verapamil (mean 439 m, p less than 0.01). Xamoterol reduced maximum walking distances as compared with verapamil (402 vs. 439 m; p less than 0.05) but not placebo (402 vs. 421 m; NSS). Thus, atenolol, verapamil, and xamoterol achieved better control of exercise-induced tachycardia than digoxin, but atenolol clearly impaired exercise tolerance whereas verapamil did not. Xamoterol achieved more even control of ventricular response rates and prevented the resting bradycardias that occurred with the other treatments. However, walking distances were significantly lower than those noted during treatment with verapamil.

Adrenergic beta-Agonists↗
PubMed1989

Atrial natriuretic factor attenuates prostaglandin E2-stimulated plasma renin activity in humans.

The effect of atrial natriuretic factor (ANF) 99-126 3 or 10 pmol/kg/min on increase in plasma renin activity (PRA) stimulated by a 30-min infusion of prostaglandin E2 (PGE2) 80 ng/kg/min was studied in healthy salt-replete male volunteers. PGE2 increased PRA to approximately 230% of basal levels (p less than 0.001). Concomitant infusion of ANF 3 pmol/kg/min significantly attenuated this rise in PRA to approximately 130% of baseline values (p = 0.02, n = 10). A quantitatively similar effect was observed with ANF 10 pmol/kg/min (n = 5). We suggest, in light of previous findings, that this inhibitory effect of ANF probably represents a nonspecific action rather than a specific effect of ANF on PGE2-mediated increases in PRA.

Adult↗
PubMed1989

Captopril: a free radical scavenger.

The use of captopril in heart failure and hypertension is becoming increasingly accepted. Captopril has a sulphydryl group in its molecular structure. We wondered if this might confer free radical scavenging activity on the drug and have investigated this in an in vitro system. Results show that captopril is a free radical scavenger and we suggest that this action might be relevant in its use in heart failure and other vascular diseases.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Evidence for a proximal and distal nephron action of atrial natriuretic factor in man.

The intrarenal mechanism of action of atrial natriuretic (ANF) remains uncertain. Animal work suggests that part of the natriuretic effect of ANF may be due to inhibition of proximal and distal nephron sodium reabsorption and we now present evidence for similar effects of ANF in man. Six sodium replete normal male volunteers were studied during maximal water diuresis. Lithium clearance was used to assess segmental nephron function. ANF infusion caused a significant increase in fractional lithium clearance (FELi) compared to placebo infusion. A similar change in fractional distal delivery, a conventional marker of proximal tubular outflow, also occurred during ANF infusion independently corroborating the increase in FELi. These findings suggest that ANF inhibits whole-kidney fractional proximal tubular sodium reabsorption in man. Evidence is also presented to show that ANF depresses distal nephron fractional sodium reabsorption as evaluated both by the lithium method and by estimation of solute-free water clearance.

Absorption↗
PubMed1989

A survey of current use of angiotensin-converting-enzyme inhibitors by Scottish physicians in the treatment of chronic cardiac failure.

318 consultant physicians in Scotland were sent a questionnaire on their use of angiotensin converting enzyme (ACE) inhibitors to treat chronic heart failure (CHF). 229 (72%) replies were received. Of these 91% used ACE inhibitors for CHF; 22% were geriatricians, 58% general physicians and 20% cardiologists. All groups reserved ACE inhibitors for patients uncontrolled by diuretics alone. Compared to general physicians, cardiologists used ACE inhibitors in preference to other vasodilators and digoxin, used higher doses and commenced treatment more often on a day-patient basis. Cardiologists also commonly started treatment with captopril even if continuing with enalapril. Geriatricians used ACE inhibitors as frequently as cardiologists but at lower doses; they did not report side-effects more frequently. Further investigation of the safety and possible cost savings of supervised day-patient rather than in-patient, introduction of ACE inhibitors for CHF is now merited. To avoid an extended period of patient observation after the first dose of ACE inhibitor, captopril might also be given as the initial therapy, even if continuing with enalapril. This policy would also reduce the risk of any hypotensive response being prolonged.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Dexamethasone suppression test in dementia and depression. Clinical and biological correlates.

To determine the usefulness of the DST in differentiating depression from dementia, the test was administered to three diagnostic groups of psychogeriatric patients: depression; dementia; and dementia with depression. Clinical assessments were supplemented by ratings on the HRSD and SCAG, as well as by EEG and CT. All three groups showed a high incidence of abnormal DST results unrelated to presence or severity of affective symptoms, but showing a better association with SCAG and its 'organic' subsets. The mechanism(s) underlying these abnormal results may reflect organic brain disease. The usefulness of the DST in differentiating depression from dementia in the elderly was not confirmed.

Aged↗
PubMed1989

Sympathoadrenal responses during bradycardia-hypotension associated with combined infusion of atrial natriuretic factor and prostaglandin E2.

The adrenergic response to an episode of bradycardia and hypotension associated with atrial natriuretic factor and prostaglandin infusion in a healthy male subject is described. Noradrenaline levels did not change despite a profound fall in blood pressure. In contrast, there was an almost thirty-fold increase in adrenaline levels. This dissociated sympathoadrenal response suggests activation of the Bezold-Jarisch reflex.

Adrenal Glands↗
PubMed1988

Frusemide pretreatment blunts the inhibition of renal tubular sodium reabsorption by ANF in man.

The effects of atrial natriuretic factor (ANF) 15 pmol/kg/min on renal function were studied in 7 normal male volunteers during maximal water diuresis. Subjects were studied in neutral salt balance either before, or after, seven days treatment with 40 mg oral frusemide. The post-frusemide state was associated with activation of the renin-angiotensin system (RAAS) and generally higher noradrenaline levels; this state was also associated with sodium retention, mainly due to enhanced distal nephron reabsorption. Without diuretic pretreatment ANF produced a natriuresis and diuresis associated with inhibition of both proximal and distal nephron sodium reabsorption. In contrast, after frusemide pretreatment, ANF caused an increase in water excretion (urinary flow rate) but no change in sodium excretion. In the post-diuretic condition ANF did not affect renal tubular handling of sodium. The enhanced tubular reabsorption of sodium post-frusemide, and the failure of ANF to suppress this, could be due to activation of the RAAS and SNS.

Adult↗
PubMed1988

Atrial natriuretic factor inhibits ACTH stimulated aldosterone, but not cortisol, secretion in man.

The effects of human ANF 99-126 on the aldosterone and cortisol responses to ACTH infusion were studied in 8 normal volunteers. ACTH infusion caused a significant rise in aldosterone and cortisol on each study day. On the day that ANF was concomitantly infused the aldosterone, but not the cortisol, response to ACTH was significantly attenuated. These results show that a pharmacological dose of ANF selectively inhibits ACTH mediated mineralocorticoid as opposed to glucocorticoid release in man. These results support in vitro and in vivo findings from animal experiments. These findings also compliment previous studies showing that ANF inhibits ANG II stimulated aldosterone release in normal subjects.

Adrenocorticotropic Hormone↗
PubMed1988

Effects of angiotensin II and atrial natriuretic peptide alone and in combination on urinary water and electrolyte excretion in man.

1. Atrial natriuretic peptide (ANP) has previously been shown to inhibit the renin-angiotensin-aldosterone system (RAAS) at several different levels. We have now investigated a further non-endocrine, renal interaction between ANP and the RAAS. 2. The effects of ANP and angiotensin II (ANG II) alone, and in combination, on urinary electrolyte and water excretion were studied in eight normal male subjects undergoing maximal water diuresis. 3. ANP caused a significant increase in urine flow and sodium excretion. ANG II alone was antidiuretic, antinatriuretic and antikaliuretic. When ANP was given against a background infusion of ANG II, urinary flow rate and electrolyte excretion increased from a new lower level to reach a value intermediate between that found with ANG II alone and ANP alone. 4. It is concluded that the renal effects of ANP are modified in the presence of simultaneously elevated levels of ANG II and that net water and electrolyte excretion reflect the sum of the opposing influences of each peptide. While this interplay may be non-specific, it is possible that ANP may exert some of its actions by specifically inhibiting the intrarenal effects of ANG II.

Adult↗
PubMed1988

Arginine vasopressin dissociates the diuresis and natriuresis due to atrial natriuretic factor in man.

The possible interaction between arginine vasopressin (AVP) and atrial natriuretic factor (ANF) in the control of urinary sodium and water excretion was investigated in man. Nine healthy male volunteers undergoing stable maximal water diuresis were studied on four separate occasions. Atrial natriuretic factor 15 pmol kg-1 min-1 or placebo (P) was concomitantly administered against a background infusion of either AVP 0.003 pmol kg-1 min-1 or P; thus the combinations P + P, AVP + P, P + ANF and AVP + ANF were studied. Atrial natriuretic factor caused a significant increase in sodium excretion (UNaV) [+56%], urinary flow rate (V) [+17%] and free water clearance (CH2O) [+23%]; creatinine clearance (Ccr) did not change. Arginine vasopressin reduced V (-58%) and CH2O (-68%) but did not alter UNaV or Ccr. On the AVP + ANF study day, UNaV increased (+64%) as with P + ANF, but V (-44%) and CH2O (-52%) continued to decrease below baseline levels; analysis of variance showed this antidiuresis reflected the prevalent effect of AVP rather than any specific interaction. These results show that AVP is able to dissociate the natriuretic and diuretic effects of ANF.

Adult↗
PubMed1988

Significance of atrial natriuretic factor in chronic heart failure.

Since the discovery by de Bold et al in 1981 of the natriuretic and diuretic properties of atrial extract a vast literature on the physiological, pharmacological and pathological aspects of atrial peptides has accumulated. In this article we review the significance of atrial natriuretic factor, endogenous and exogenously administered, in chronic heart failure.

Atrial Natriuretic Factor↗
PubMed1988

The effect of atrial natriuretic factor on urinary albumin and beta 2-microglobulin excretion in man.

The effect of a 20-min infusion of atrial natriuretic factor (ANF) 99-126, 0.4 microgram/kg per min, on both urinary albumin and beta 2-microglobulin excretion was examined in nine normal male subjects during stable water diuresis. ANF caused a rise in urinary albumin in excretion (from 4.19 +/- 0.66 to 13.49 +/- 3.07 ng/min, P less than 0.01) without any significant change in either creatinine clearance of beta 2-microglobulin excretion. These findings suggest that ANF may enhance glomerular permeability to albumin in man.

Adult↗