Diuretics and oedema: how to avoid rebound sodium retention.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
G A MacGregor
Publications and source records attributed to G A MacGregor.
Blood pressure, angiotensin-converting enzyme (ACE) inhibitors, and the kidney.
Angiotensin II plays an important role in the kidney by regulating renal flow, glomerular filtration rate, mesangial cell function, and sodium reabsorption. Blockade of the renin-angiotensin system has powerful effects on kidney function. Studies in animal models of renal failure suggest that converting enzyme inhibitors slow down the inevitable progression of the renal failure. This could be in part due to their effect on reducing glomerular pressure or by reducing glomerular hypertrophy. In patients with malignant hypertension, diabetic nephropathy, and other causes of renal failure, preliminary evidence suggests that lowering the blood pressure with angiotensin-converting enzyme (ACE) inhibitors may possibly carry some other benefits compared with other blood pressure lowering regimens. However, single drug therapy is rarely sufficient to control blood pressure in these patients. Further properly controlled randomized trials should give a clear indication of whether any particular class of drug has any advantage in slowing down the progressive renal impairment for a given lowering of blood pressure. In patients with renovascular hypertension ACE inhibitors are effective drugs in lowering blood pressure. However, in certain settings they may cause a reversible decline in renal function.
Angiotensin II↗
Plasma concentrations and comparisons of brain natriuretic peptide and atrial natriuretic peptide in normal subjects, cardiac transplant recipients and patients with dialysis-independent or dialysis-dependent chronic renal failure.
1. We have developed a radioimmunoassay for the measurement of immunoreactive brain natriuretic peptide (1-32) in human plasma. Simultaneous measurements of atrial natriuretic peptide have also been carried out to allow for direct comparison between circulating brain natriuretic peptide and atrial natriuretic peptide. Plasma levels of immunoreactive brain natriuretic peptide (means +/- SEM) were 1.1 +/- 0.1 pmol/l in 36 normal healthy subjects and were significantly elevated in cardiac transplant recipients (18.8 +/- 3.9 pmol/l, n = 12) and in patients with dialysis-independent (8.8 +/- 1.5 pmol/l, n = 11) or dialysis-dependent (41.6 +/- 8.8 pmol/l, n = 14) chronic renal failure. Similarly, in these groups of patients plasma levels of atrial natriuretic peptide were also significantly raised when compared with those in the group of normal healthy subjects. 2. The plasma level of atrial natriuretic peptide was significantly higher than that of brain natriuretic peptide in normal subjects and in patients with dialysis-independent chronic renal failure, with ratios (atrial natriuretic peptide/brain natriuretic peptide) of 2.8 +/- 0.2 and 2.2 +/- 0.3, respectively. However, in both cardiac transplant recipients and patients on dialysis plasma levels of atrial natriuretic peptide and brain natriuretic peptide were similar, with ratios of 1.3 +/- 0.2 and 1.0 +/- 0.1, respectively, in these two groups. 3. Plasma levels of brain natriuretic peptide and atrial natriuretic peptide were significantly correlated in the healthy subjects and within each group of patients. When all groups were taken together, there was an overall correlation of 0.90 (P < 0.001, n = 73).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Is atrial natriuretic peptide-guanosine 3',5' cyclic monophosphate coupling a determinant of urinary sodium excretion in essential hypertension?
OBJECTIVES: (1) To compare urinary guanosine 3',5' cyclic monophosphate (cyclic GMP) excretion between normotensive subjects and essential hypertensive patients; (2) to determine the influence of changes in sodium intake on urinary cyclic GMP excretion in response to the neutral endopeptidase inhibitor candoxatril in essential hypertensives. DESIGN: (1) Twenty-five normotensive subjects and 25 patients with established essential hypertension not on treatment; (2) Single oral dose of candoxatril in eight patients with essential hypertension after equilibration on a low- or high-sodium diet in a placebo-controlled, double-blind, randomized, crossover study. METHODS: Blood pressure was measured by ultrasound sphygmomanometry. Atrial natriuretic peptide (ANP) and urinary cyclic GMP were measured by radioimmunoassay. Group comparisons were made using unpaired t-tests and two-way analysis of variance. RESULTS: Plasma ANP was significantly raised in patients with essential hypertension compared with the normotensive group, but there was no difference in urinary cyclic GMP excretion. Plasma ANP increased significantly on the high- compared with low-sodium diet. After candoxatril, there were significant diet-related increases in plasma ANP and urinary sodium excretion up to 6 h after drug administration. There were similar increases in urinary cyclic GMP excretion on both diets, but there were no consistent differences in this excretion between the low- and high-sodium diets. CONCLUSIONS: These observations not only point to the importance of ANP-cyclic GMP coupling as a determinant of the natriuretic response to endopeptidase inhibition, but also suggest that the excretion of urinary cyclic GMP can be influenced by other factors in addition to circulating ANP.
Atrial Natriuretic Factor↗
Humoral effects of perindopril in essential hypertension.
Explore the source record for details and available documents.
Angiotensin-Converting Enzyme Inhibitors↗
Acute and sustained changes in sodium balance during nifedipine treatment in essential hypertension.
PURPOSE: To assess the changes in sodium excretion and sodium balance after initiation of nifedipine treatment and after withdrawal of nifedipine. PATIENTS: Eight patients with uncomplicated mild to moderate essential hypertension were entered in a single-blind, placebo-controlled study of 39 days' duration. METHODS: Two 7-day periods while on a fixed sodium intake of 150 mmol/day approximately 3 weeks apart. After 4 days of a placebo and fixed sodium intake, patients were given nifedipine GITS (gastrointestinal therapeutic system) once a day and carefully studied for the following 4 days. Thereafter, patients continued to receive nifedipine GITS, and approximately 3 weeks later they were studied again for a week while on a fixed sodium intake. Nifedipine administration was stopped and changes occurring after withdrawal were studied. RESULTS: Nifedipine caused a significant increase in sodium excretion with a cumulative loss of sodium of 38 mmol per subject within the first 4 days of treatment. The withdrawal of nifedipine treatment caused a significant decrease in sodium excretion and a cumulative retention of sodium of 42 mmol per subject within the first 4 days of withdrawal. CONCLUSION: Nifedipine causes an acute and a sustained reduction in sodium balance in patients with essential hypertension. This prolonged effect may contribute to the mechanism whereby nifedipine lowers blood pressure.
Aged↗
How important are suppression of aldosterone and stimulation of atrial natriuretic peptide secretion in the natriuretic response to an acute sodium load in man?
1. Aldosterone is suppressed by sodium loading. We studied the contribution of this decrease in plasma aldosterone to the natriuresis after acute sodium loading in healthy volunteers. 2. Two litres of saline [0.9% (w/v) NaCl] were infused during the second hour of a 6 h infusion of aldosterone (3 pmol min-1 kg-1) or placebo in eight healthy young men. On the placebo day, plasma aldosterone decreased by 30 min after the start of saline infusion and remained suppressed. During aldosterone infusion, plasma aldosterone was maintained at around 400 pmol/l. 3. Urinary sodium excretion, lithium clearance and plasma atrial natriuretic peptide increased and plasma renin activity decreased after saline infusion, whether or not aldosterone was infused. However, from 60 to 240 min after saline infusion, natriuresis was significantly less during aldosterone infusion than on the placebo day. In addition, saline loading led to a progressive increase in the ratio of sodium clearance to lithium clearance, used as an index of the fractional distal tubular rejection of sodium, and in the ratio of urinary sodium to potassium. These increases were prevented by the infusion of aldosterone. 4. This study suggests that there are differences in the mechanisms determining the early and the later responses to an acute sodium load. Suppression of aldosterone may explain much of the later increase in natriuresis after saline infusion. In addition, the results are consistent with a role for atrial natriuretic peptide in the immediate increase in sodium excretion after saline loading.
Adult↗
Effect of a single test dose of lithium carbonate on sodium and potassium excretion in man.
1. The possible natriuretic and kaliuretic effects of a single dose of lithium, as used in lithium clearance studies, were investigated in 15 healthy subjects on fixed sodium (100 mmol/24 h) and potassium (70 mmol/24 h) intakes. Lithium carbonate (300 mg or 600 mg) or placebo tablets were administered, double-blind and in random order, midway through a 48 h urine collection (divided into six 8 h periods), at 23.00 hours. 2. During the three 24 h periods which preceded the administration of lithium or placebo (control days), rates of sodium and potassium excretion followed normal circadian patterns, but no differences in excretion rates between the 3 control days were observed. Placebo tablets did not affect excretion rates. 3. After the 300 mg dose of lithium carbonate, 24 h sodium excretion increased by approximately 17 mmol (P less than 0.05); almost all of the natriuretic effect occurred during the first two 8 h periods. No effect on potassium excretion was observed. 4. After the 600 mg dose of lithium carbonate, 24 h sodium excretion increased by approximately 48 mmol (P less than 0.001) and 24 h potassium excretion increased by approximately 19 mmol (P less than 0.01). These effects were confined to the first two 8 h periods and thus occurred before and during the usual lithium clearance period. 5. Plasma renin activity, measured in 10 subjects, increased after the 600 mg dose of lithium carbonate (P less than 0.005), but plasma concentrations of aldosterone and atrial natriuretic peptide were not significantly affected. Neither the 300 mg dose of lithium carbonate nor the placebo tablets affected hormone levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
A double-blind crossover study of the effect of concomitant diuretic therapy in hypertensive patients treated with amlodipine.
Twelve patients with essential hypertension who were already on treatment with the long-acting calcium antagonist amlodipine (5 mg once daily) were entered into a double-blind, randomized crossover study of the addition of one month's treatment with either bendrofluazide (5 mg once daily) or matching placebo. The addition of bendrofluazide did not cause any statistically significant fall in the supine blood pressure compared to treatment with placebo (147.6/90.1 +/- 4.8/2.8 v 150.8/92.6 +/- 4.3/2.3 mm Hg, respectively). Plasma potassium was significantly lower on bendrofluazide as compared to placebo (3.11 +/- 0.14 v 3.62v +/- 0.13 mmol/L, P less than .001) and 10 of 12 patients had a fall in plasma potassium while on diuretic. The results of this study suggest that a thiazide diuretic has little additive effect on blood pressure in patients already on the long-acting dihydropyridine amlodipine, and may cause hypokalemia.
Adult↗
Does potassium supplementation lower blood pressure? A meta-analysis of published trials.
Both epidemiologic and clinical studies have suggested that an increase in potassium intake may lower blood pressure. However, the results of prospective clinical trials looking at the effect of oral potassium supplements on blood pressure have yielded conflicting results. For this reason, we reviewed 19 clinical trials examining the same end-point and involving a total of 586 participants (412 of whom had essential hypertension). Overall, the results of the trials indicate that oral potassium supplements significantly lower systolic blood pressure [-5.9 mmHg, -6.6 to -5.2 mmHg (mean, 95% confidence interval)] and diastolic blood pressure (-3.4 mmHg, -4.0 to 2.8 mmHg). The magnitude of the blood pressure lowering effect is greater in patients with high blood pressure (-8.2 mmHg, -9.1 to -7.3 mmHg for systolic and -4.5 mmHg, -5.2 to -3.8 mmHg for diastolic blood pressure) and appears to be more pronounced the longer the duration of the supplementation (P less than 0.05 and P less than 0.01 for systolic and diastolic, respectively). Based on this analysis, an increase in potassium intake should be included in the recommendations for a non-pharmacological approach to the control of blood pressure in uncomplicated essential hypertension.
Adult↗
Leucocyte intracellular pH and Na(+)-H+ exchange activity in essential hypertension: an in vitro study under physiological conditions.
The cellular basis for essential hypertension remains obscure. Abnormal ion transport has been demonstrated in both experimental and essential hypertension, raised levels of sodium-lithium (Na(+)-Li+) and sodium-proton (Na(+)-H+) exchange in blood cells being a consistent feature. However, Na(+)-H+ exchange is not the main regulator of intracellular pH at resting pH, while the importance of the contribution of bicarbonate to cellular pH regulation is now increasingly appreciated. Serum and serum-derived growth factors are known to affect intracellular pH and the activity of the Na(+)-H+ antiporter. This study was designed to investigate the activity of Na(+)-H+ exchange in the leucocytes of patients with essential hypertension in the presence of bicarbonate in vitro and to measure the effect of autologous serum on intracellular pH and Na(+)-H+ exchange. Paired serum samples from essential hypertensives and their controls were used on leucocytes from other (unrelated, normotensive) donors to investigate the same parameters. In a study of 30 patients with untreated essential hypertension and 30 controls matched for age, sex, race and body habitus we found no difference in resting pH or buffering capacity (pH 7.28 +/- 0.01 and 32.0 +/- 1.6 mmol/l per pH, hypertensives, versus 7.27 +/- 0.02 and 34.5 +/- 1.8 mmol/l per pH, controls) but a marked difference in the maximal rate of Na(+)-H+ exchange in response to intracellular acidification (57.8 +/- 3.2 mmol/l per min versus 47.2 +/- 1.4 mmol/l per min, P = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Renal tubular sodium handling and plasma atrial natriuretic peptide, renin activity and aldosterone in untreated men under normal living conditions.
The associations between renal tubular sodium handling and plasma levels of atrial natriuretic peptide, renin activity and aldosterone were studied in 295 untreated men under normal living conditions. The renal clearance of ingested lithium was used as a marker of proximal tubular sodium handling. Plasma atrial natriuretic peptide was inversely related to creatinine clearance (r = -0.148, P less than 0.01) and directly and significantly related to the overall fractional excretion of sodium (r = 0.213, P less than 0.001) and to distal (r = 0.151, P less than 0.01) fractional sodium excretion. Plasma renin activity was inversely related to sodium excretion at both proximal (r = -0.145, P less than 0.05) and distal (r = -0.236, P less than 0.001) tubular site, whereas plasma aldosterone was significantly and inversely related to distal sodium excretion only (r = -0.305, P less than 0.001). The association between plasma atrial natriuretic peptide and distal sodium excretion in a large sample of men under normal living conditions supports the view of a possible tubular effect of the hormone of the overall control of sodium excretion in man.
Adult↗
Atrial natriuretic peptide, aldosterone, and plasma renin activity in peripartum heart failure.
Plasma concentrations of atrial natriuretic peptide and aldosterone and plasma renin activity were measured in patients with peripartum heart failure and in age matched healthy women post partum. Both groups had carried out traditional postpartum practices of salt consumption and body heating. Plasma concentrations (mean (SEM)) of atrial natriuretic peptide were significantly higher in the seven patients with peripartum heart failure (146.9 (24.3) pg/ml) than in the seven controls (4.4 (0.8) pg/ml). Both plasma aldosterone and plasma renin activity were suppressed in the patients with peripartum heart failure. After treatment for the heart failure plasma atrial natriuretic peptide fell considerably and there were associated increases in plasma aldosterone and plasma renin activity. The high plasma concentrations of atrial natriuretic peptide may have been a compensatory response to salt and water retention as well as to the heart failure. These high concentrations could also, in part, have suppressed the release of aldosterone and renin in an attempt to correct for volume overload.
Adult↗
Atrial natriuretic peptides in essential hypertension: basal plasma levels and relationship to sodium balance.
The identification of the atrial natriuretic peptides (ANP) as a new hormonal system has provided a new perspective on the mechanisms controlling renal sodium excretion and abnormalities in sodium homeostasis. The present article focuses on the potential importance of ANP (ANF 99-126) in essential hypertension with particular reference to circulating ANP levels and the relationship between the ANP and the renin-angiotensin system in the control of sodium balance and blood pressure. There is now considerable evidence demonstrating that a substantial proportion of patients with essential hypertension have raised circulating ANP levels. Given the known biological actions of ANP, these raised levels point to important compensatory mechanisms. This is further supported by studies during alterations in dietary sodium intake, as sodium restriction high-lighted important relationships between ANP and the renin angiotensin system. The potential importance of ANP in essential hypertension is strengthened by recent demonstration of natriuretic and antihypertensive actions associated with small increases in circulating ANP as induced by administration of exogenous ANP. Furthermore, the recent development of orally active inhibitors of ANP metabolism now provides a basis to determine the therapeutic importance of specific manipulation of endogenous ANP levels in patients with essential hypertension.
Animals↗
Dietary sodium and inhibition of neutral endopeptidase 24.11 in essential hypertension.
Basal atrial natriuretic peptide levels and the response to exogenous atrial natriuretic peptide are influenced by dietary sodium intake. In view of interest in the therapeutic potential of elevating plasma atrial natriuretic peptide by inhibition of neutral endopeptidase 24.11, we studied the renal and hormonal effects of 200 mg of the oral endopeptidase 24.11 inhibitor candoxatril in eight patients with untreated essential hypertension on high sodium (350 mmol/day) and low sodium (10 mmol/day) diets. With endopeptidase 24.11 inhibition, plasma atrial natriuretic peptide increased more than twofold on low and high sodium diets (p less than 0.05). Plasma N-terminal pro-atrial natriuretic peptide increased on the high sodium intake but was unaffected by candoxatril. Urinary sodium excretion increased threefold on the low sodium and sixfold on the high sodium diet (p less than 0.05). The absolute increase in urinary sodium excretion during the 24 hours after treatment compared with placebo was 18 +/- 8 mmol on the low sodium and 98 +/- 34 mmol on the high sodium diet (p less than 0.05). Plasma renin activity was suppressed by treatment on the low but not on the high sodium diet (p less than 0.05). Blood pressure did not change in the 6 hours after a single dose of candoxatril. These findings show that sodium intake is a major determinant of the response to endopeptidase 24.11 inhibition. The lack of effect on N-terminal pro-atrial natriuretic peptide suggests that candoxatril does not influence cardiac secretion of atrial natriuretic peptide or catabolism of N-terminal pro-atrial natriuretic peptide, and the latter does not appear to play a role in the response to candoxatril.
Adult↗
Combination therapy in hypertension.
There is controversy as to which BP-lowering manoeuvres and/or drugs can be combined effectively. Ideally, a combination therapy should show an additional BP-lowering effect over monotherapy. The effect should be of sufficient clinical significance, without short- or long-term adverse effects, and the patients should feel well. Combination therapy should be based on the understanding of the mechanisms of action of the different classes of drugs used and of their interaction. Rational combinations include an ACE inhibitor or a beta-blocker together with moderate salt restriction or a thiazide diuretic or a calcium antagonist. Less rational combinations include an ACE inhibitor with a beta-blocker, and a calcium antagonist with a thiazide diuretic.
Adrenergic beta-Antagonists↗
Studies of captopril alone and in combination with the benzothiazepine diltiazem or the dihydropyridine nifedipine in treating essential hypertension.
Calcium antagonists and converting enzyme inhibitors are now widely used as first line therapy for high blood pressure. This gradual move from the diuretics and beta-blockers is, in part, due to fewer or different side effects and the perceived lack of deleterious metabolic effects. Calcium antagonists may be more effective in elderly and low-renin patients. However, this is likely to be due in part to the finding that calcium antagonists are more effective with a higher initial pressure. The efficacy of converting enzyme inhibitors is related to the initial level of plasma angiotensin II (Ang II) or plasma renin activity. However, patients with low plasma renin activity also have a fall in blood pressure with converting enzyme inhibitors, illustrating the importance of differences in Ang II receptor sensitivity to the prevailing level of Ang II. Many patients require the combination of more than one drug to control their blood pressure. Combining a converting enzyme inhibitor with either a dihydropyridine or a benzothiazepine calcium antagonist is a particularly effective approach to the treatment of patients with more severe essential hypertension.
Adult↗
Moderate potassium supplementation in hypertension: how useful?
Explore the source record for details and available documents.
Adult↗