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Biomedical subjects

A D Struthers

Publications and source records attributed to A D Struthers.

At least 235 records · Page 13Linked to original sources
PubMed1989

Atrial natriuretic factor inhibits isoproterenol- and furosemide-stimulated renin release in humans.

The effects of atrial natriuretic factor (0.025 microgram/kg/min) on isoproterenol-(0.02 microgram/kg/min) and furosemide-(5 mg i.v. bolus) stimulated renin release were studied in seven salt-replete healthy volunteers. Isoproterenol or furosemide were given against a background infusion of 5% D-glucose (placebo day) or atrial natriuretic factor (experimental day). Atrial natriuretic factor abolished the rise in plasma renin activity caused by isoproterenol (p = 0.003) and significantly (p = 0.048) attenuated the rise in plasma renin activity after a bolus injection of furosemide. These results show that a pharmacological dose of atrial natriuretic factor inhibits stimulated renin release in humans. This attenuation is apparent with two heterogenous stimuli, which suggests a nonspecific effect.

Adult↗
PubMed1989

Tachyphylaxis to systemic but not to airway responses during prolonged therapy with high dose inhaled salbutamol in asthmatics.

High doses of inhaled salbutamol produce substantial improvements in airway response in patients with asthma, and are associated with dose-dependent systemic beta-adrenoceptor responses. The purpose of the present study was to investigate whether tachyphylaxis occurs during prolonged treatment with high dose inhaled salbutamol. Twelve asthmatic patients (FEV1, 81 +/- 4% predicted), requiring only occasional inhaled beta-agonists as their sole therapy, were given a 14-day treatment with high dose inhaled salbutamol (HDS), 4,000 micrograms daily, low dose inhaled salbutamol (LDS), 800 micrograms daily, or placebo (PI) by metered-dose inhaler in a double-blind, randomized crossover design. During the 14-day run-in and during washout periods, inhaled beta-agonists were withheld and ipratropium bromide was substituted for rescue purposes. At the end of each 14-day treatment, a dose-response curve (DRC) was performed, and airway (FEV1, FEF25-75) chronotropic (HR), tremor, and metabolic (K, Glu) responses were measured at each step (from 100 to 4,000 micrograms). Treatment had no significant effect on baseline values. There were dose-dependent increases in FEV1 and FEF25-75 (p less than 0.001), and pretreatment with HDS did not displace the DRC to the right. DRC for HR (p less than 0.001), K (p less than 0.001), and Glu (p less than 0.005) were attenuated after treatment with HDS compared with PI. There were also differences between HDS and LDS for HR (p less than 0.001) and Glu (p less than 0.05) responses. Frequency and severity of subjective adverse effects were also reduced after HDS: tremor (p less than 0.001), palpitations (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
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

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↗
PubMed1989

Development of persistent late onset asthma following treatment with captopril.

We describe the first case of de novo asthma following treatment with the angiotensin converting enzyme (ACE) inhibitor captopril. Despite drug withdrawal there was evidence of persistent airways obstruction and bronchial hyperreactivity. This suggests the possibility that ACE inhibitors may uncover an asthmatic tendency in patients with pre-existing bronchial hyperreactivity.

Aged↗
PubMed1988

Respiratory function measurements in clinical pharmacological studies including an assessment of the area under the MEFV curve as a new parameter in chronic bronchitic patients.

We have assessed the value of the area under the MEFV curve (AUC) as an index of respiratory function in chronic bronchitis and compared it with PFR, FEV1, FVC, volume at 75% PFR (V75), V50, V25, F50 and F75. The reproducibility of these parameters was tested in 10 normal subjects and 10 patients with chronic bronchitis. The FVC was the most reproducible while the coefficient of variation for the AUC was the same as for the other MEFV curve indices. The sensitivity (percentage change on bronchodilatation after intravenous aminophylline) of the above measurements was also tested in a further nine patients with chronic bronchitis. The AUC was much more sensitive to bronchodilatation than any of the other measurements. Therefore although the AUC was less reproducible than simple spirometric indices, it was more sensitive to bronchodilatation by a greater factor. This probably outweighs its poor reproducibility and AUC would therefore seem to be a useful new index of bronchodilatation in chronic bronchitis.

Adult↗
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

Rapid changes in plasma potassium during a game of squash.

1. The game of squash has recently been associated with a high incidence of ventricular arrhythmias and sudden death. To investigate this further, plasma catecholamines and potassium (K+) were monitored during a game of squash in six normal volunteers. 2. No cardiac arrhythmias were seen in this study despite the subjects reaching maximum heart rates of 181 +/- 5 beats/min (mean +/- SEM). 3. During exercise, plasma K+ rose from 3.82 +/- 0.16 to 4.29 +/- 0.2 mmol/l, but after 90 s rest this fell to 3.68 +/- 0.28 mmol/l and after 180 s to 3.44 +/- 0.17 mmol/l. This rapid K+ shift could not be accounted for by generalized changes in venous acid-base status or by changes in venous plasma catecholamines. Although pretreatment with a beta 2-antagonist caused the overall plasma K+ levels to be higher, it had no significant effect on the fall in plasma K+ after exercise. 4. Such rapid K+ shifts after exercise might contribute to arrhythmogenesis in susceptible individuals. The precise mechanism of the fall in K+ after exercise remains undetermined, but it seems not to involve catecholamines stimulating beta 2-adrenoceptors and is more likely to be due to increased skeletal muscle blood flow and/or intracellular acidosis.

Adrenergic beta-Antagonists↗
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

Physiological increases in circulating noradrenaline are antinatriuretic in man.

Low-dose (0.025 micrograms/kg per min) noradrenaline infusion, resulting in a physiological plasma increment (280 pg/ml), was antinatriuretic in normal salt-replete male subjects. The reduction in sodium excretion (-20%, P less than 0.01) occurred without any change in the glomerular filtration rate but was associated with a significant (P less than 0.02) decline in lithium clearance. These results suggest that changes in circulating noradrenaline, within the physiological range, can decrease sodium excretion in man by enhancing proximal tubular sodium reabsorption. These findings extend previous investigations in man which used pharmacological doses of noradrenaline and are in agreement with animal evidence for a renal tubular antinatriuretic effect of the sympathetic nervous system.

Adult↗
PubMed1988

Sympathetically mediated vasoconstriction is augmented by angiotensin II in man.

In order to determine whether angiotensin II may influence sympathetically mediated arteriolar constriction in man, we have examined the effect of angiotensin II, infused directly into the left brachial artery of normal subjects, on the reduction in forearm blood flow produced by a lower-body negative pressure (LBNP) of 15 mmHg. Angiotensin II (320 fmol/min) caused no reduction in blood flow when given alone but significantly augmented the reduction in blood flow in response to LBNP. The same dose of angiotensin II did not affect a similar reduction in forearm blood flow produced by infused noradrenaline (12.5-50 ng/min). We conclude that angiotensin II augments sympathetically mediated constriction of resistance vessels in man at concentrations with no direct effect on vessel tone. The lack of an effect of angiotensin II on constriction in response to infused noradrenaline suggests the involvement of a presynaptic mechanism.

Angiotensin II↗
PubMed1988

The effect of prazosin on skin microcirculation as assessed by laser Doppler flowmetry.

1. Laser Doppler flowmetry was used in six normal volunteers to record changes in fingertip skin blood flow after the administration of prazosin to block postsynaptic alpha 1-adrenoceptors. 2. Prazosin (0.5 mg orally) did not alter systolic or diastolic blood pressure or heart rate. 3. Prazosin did significantly increase basal skin blood flow 2 h after its administration but this effect was no longer evident after contralateral hand warming. Prazosin markedly reduced the skin vasoconstrictor response to deep inspiration and to contralateral hand cooling. 4. This study suggests that postsynaptic alpha 1-adrenoceptors are involved in maintaining skin vasoconstrictor tone at rest and are also involved in the rapid skin vasoconstriction seen in response to a deep inspiration and to contralateral hand cooling.

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

Regulation of regional vascular tone: the role of angiotensin conversion in human forearm resistance vessels.

Inhibition of the action of endothelially-located angiotensin converting enzyme (ACE) in blood vessels of the human forearm was studied using enalaprilat, the active metabolite of the prodrug enalapril. In a dose of 5 micrograms/min enalaprilat inhibits arteriolar vasoconstriction in response to angiotensin I (Ang I) and enhances vasodilation in response to bradykinin. At this dose enalaprilat had no effect on resting forearm blood flow, or on the reduction in forearm blood flow in response to application of lower body negative pressure, in subjects with normal sodium intake. Following sodium depletion, however, enalaprilat produced an increase in resting forearm blood flow compared with the response in the same subjects under normal-sodium conditions. It appears that local ACE within forearm resistance vessels of healthy volunteers is unlikely to play an important role in regulation of local vascular tone in the sodium-replete state. However, in sodium-depleted subjects, and perhaps also in other circumstances where circulating concentrations of Ang I are elevated, local ACE may significantly affect vascular tone.

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↗