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Biomedical subjects

N D Markandu

Publications and source records attributed to N D Markandu.

At least 37 records · Page 2Linked to original sources
PubMed1998

Importance of the renin system in determining blood pressure fall with salt restriction in black and white hypertensives.

Seventy-one white and 33 black patients with essential hypertension were studied while on a high sodium intake of 350 mmol/d for 5 days and low sodium intake of 10 mmol/d for 5 days. The fall in blood pressure on changing from the high sodium to the low sodium diet was 17/6 mm Hg in whites and 22/10 mm Hg in blacks. Compared with whites, black patients had a 7-mm Hg greater fall (P<0.05) in systolic blood pressure and 4-mm Hg greater fall (P=0.068) in diastolic blood pressure (adjusted for age and blood pressure on the normal diet) with similar changes in urinary sodium excretion. With sodium restriction, plasma renin activity rose from 0.65 to 3.03 ng. mL-1. h-1 in whites, whereas in blacks it rose only from 0.3 to 1.28 ng. mL-1. h-1 (P<0.001 between blacks and whites). From the high to the low salt diet, plasma angiotensin II increased by 31 pmol/L in whites and by 12 pmol/L in blacks (P<0.05 compared with whites), and plasma aldosterone rose by 499 pmol/L in whites and by 256 pmol/L in blacks (P<0.01). Significant inverse correlations were obtained for all patients between the fall in systolic blood pressure from the high to low salt diet and the rise in plasma renin activity and angiotensin II, as well as the absolute level on the low salt diet. These results demonstrate that the larger fall in blood pressure with a reduction in salt intake in blacks is due at least in part to a less responsive renin-angiotensin-aldosterone system in blacks.

Adult↗
PubMed1997

Double-blind randomised trial of modest salt restriction in older people.

BACKGROUND: Stroke is directly related to blood pressure and treatment trials in older hypertensive individuals show a reduction in strokes. However, the majority of strokes occur in normotensive individuals in whom no attempt is made to lower blood pressure. We compared the effects of modest salt restriction on blood pressure in older hypertensive and normotensive people. METHODS: 47 untreated elderly people (24 men, age range 60-78 years; blood-pressure range 123-205 mm Hg systolic and 64-112 mm Hg diastolic) completed a 2-month double-blind randomised placebo-controlled crossover study of modest salt restriction with slow sodium and placebo to give a salt intake of either 10 g (equivalent to the normal amount for the UK population) or 5 g. FINDINGS: On the normal salt intake for the UK population, supine blood pressure was 163/90 (SD 21/10) mm Hg with urinary sodium excretion of 177 (49) mmol/day. With modest sodium restriction, blood pressure fell to 156/87 (22/9) mm Hg (p < 0.001/0.004) with a urinary sodium excretion of 94 (50) mmol/day. A reduction in sodium intake of 83 mmol/day was associated with a reduction of 7.2/3.2 mm Hg. There was no significant difference in the blood-pressure fall between 18 normotensive and 29 hypertensive participants (8.2/3.9 vs 6.6/2.7 mm Hg). INTERPRETATION: A modest reduction in salt intake leads to a fall in blood pressure in both normotensive and hypertensive older people similar to that in outcome trials of thiazide-based treatment. Since the majority of strokes in older people occur below the current definition of hypertension, our results have important implications for the prevention of stroke.

Aged↗
PubMed1996

A diuretic is more effective than a beta-blocker in hypertensive patients not controlled on amlodipine and lisinopril.

The combination of an angiotensin-converting enzyme inhibitor and a calcium antagonist has a synergistic effect in patients with more severe hypertension. However, when this combination fails to control blood pressure, it is not clear which drug is then additive. The aim of this work was to study in a double-blind, randomized, crossover design the effect on blood pressure of the addition of either a thiazide diuretic (bendrofluazide, 5 mg once daily) or a beta-blocker (atenolol, 100 mg once daily) or placebo each for a month in hypertensive patients who are not adequately controlled on the combined treatment of amlodipine 5 mg once daily and lisinopril 5 mg twice daily. Eighteen patients with a supine diastolic pressure of more than 90 mm Hg after at least 1 month on the combined treatment of amlodipine and lisinopril were enrolled in the study. The results show that in patients whose blood pressures are not controlled by the combination of amlodipine and lisinopril, the addition of bendrofluazide 5 mg once daily causes a significant fall in blood pressure compared with placebo and a significantly greater fall than 100 mg atenolol once daily.

Adrenergic beta-Antagonists↗
PubMed1996

Angiotensin converting enzyme gene I/D polymorphism, blood pressure and the renin-angiotensin system in Caucasian and Afro-Caribbean peoples.

The objectives of this study were to assess relations between ACE gene I/D polymorphism, essential hypertension, plasma renin activity and aldosterone in white (European descent) and black (Afro-Caribbean descent) peoples. Measurements were carried out on a total of 320 subjects (210 white: 116 men, 94 women; 110 black: 65 men, 45 women); all were on their usual sodium intake; none was on anti-hypertensive therapy and none had secondary hypertension. Genomic DNA was isolated from blood cells and ACE I/D genotype was established using polymerase chain reaction. Plasma hormones were measured by radioimmunoassay and blood pressure (BP) with an ultrasound sphygmomanometer. All subjects were grouped into normotensive, borderline and hypertensive according to WHO guidelines. The distribution of the I/D genotype in the white people was approximately 1:2:1; by contrast, in the Afro-Caribbean people there was a significantly higher frequency of the D allele (chi 2P = 0.04). Within the white people there was no significant association between ACE genotype and high BP; however, within the black people there was a positive association between the frequency of the D allele and increasing BP ( chi 2 for trend P = 0.03). In either group, there were no associations between ACE I/D genotype and plasma renin activity and aldosterone suggesting that ACE genotype does not contribute to the expression of the circulating renin-angiotensin system. This study highlights differences in ACE I/D polymorphism between white and black peoples and suggests the possibility of racial differences in the association between ACE genotype and BP.

Adult↗
PubMed1996

Echocardiography overestimates left ventricular mass: a comparative study with magnetic resonance imaging in patients with hypertension.

OBJECTIVE: To compare measurement of left ventricular mass (LVM) by M-mode echocardiography and magnetic resonance imaging (MRI) in hypertensive subjects. DESIGN: A prospective study. SUBJECTS: Twenty-four untreated hypertensive patients [19 men and five women, aged 51 +/- 2 (mean +/- SEM) years, supine blood pressure 159/101 +/- 3/1 mmHg]. SETTING: The Blood Pressure Unit, St Georges Hospital Medical School and Magnetic Resonance Unit, Royal Brompton National Heart and Lung Hospital, London. MAIN OUTCOME MEASURES: LVM estimated both by M-mode echocardiography and by MRI. RESULTS: Using three standard M-mode formulae, widely different values of LVM were obtained with echocardiography [American Society of Echocardiography (ASE) 319 +/- 21 g, Penn 273 +/- 19 g. Teichholz 191 +/- 11 g]. By MRI, the LVM was 232 +/- 11 g. The differences between MRI and echocardiography could not be explained in terms of the timing of measurements in the cardiac cycle. When single-slice MRI measurements at the appropriate level were applied to the ASE and Penn formulae, the LVM was again overestimated. CONCLUSION: Our study has shown major differences in LVM estimated using methods based on one-dimensional (echocardiography) compared with three-dimensional (MRI) data. These differences seem to be largely the result of the geometrical assumptions on which M-mode measurements are based. Our findings have important clinical implications for the assessment of the severity and response to treatment of left ventricular hypertrophy in hypertensive patients.

Echocardiography↗
PubMed1996

Glucose load and renal sodium handling in mild essential hypertension on different sodium intakes.

The aims of the present study were to investigate the effects of changes in sodium intake in patients with untreated mild essential hypertension on the hormonal (plasma renin activity and aldosterone) and renal tubular responses to short-term hyperinsulinemia as achieved by an oral glucose tolerance test (OGTT). Fourteen patients with essential hypertension (mean age, 46 years; average blood pressure (BP), 151/96 mm Hg) were studied. After a 1 week run-in period on their usual diet they entered a randomized double-blind crossover study of a week of low (10 mmol/day) vs a week of high (350 mmol/day) sodium intake. On the last day of each diet they underwent a standard 2-h OGTT. Blood and urines were taken hourly and segmental tubular sodium handling was assessed by the endogenous lithium clearance. The results demonstrate that the plasma insulin and glucose response to a short-term oral glucose load were not influenced significantly by the changes in dietary sodium intake. However, the glucose load was associated with marked renal sodium retention in the absence of any change in systemic BP. The reduction in renal sodium excretion was independent of circulating aldosterone but appeared to be due to an increase in renal distal tubular re-absorption.

Adolescent↗
PubMed1995

Hormonal and renal responses to neutral endopeptidase inhibition in normal humans on a low and on a high sodium intake.

Hormonal and renal effects of candoxatril, a neutral endopeptidase 24.11 inhibitor, were investigated in eight subjects equilibrated on a low sodium diet (10 mmol sodium per day) and a high sodium (350 mmol per day) diet. After candoxatril treatment, plasma ANP increased to a maximum at 2-4 h and declined to baseline within 24 h. The increases were relatively greater on the high sodium diet, which was also associated with increases in urinary sodium, with highest values at 4h. On the low sodium diet, the magnitude of the changes was significantly lower (24 h cumulative sodium excretion was 11.4 +/- 5.5 mmol on the low sodium diet and 73.1 +/- 25.6 mmol on the high sodium diet; P < 0.01). There were no significant effects on urinary potassium excretion, creatinine clearance or haematocrit. After candoxatril treatment there were reductions in PRA, especially on the low sodium diet. On either diet there were no effects on systemic blood pressure. These results demonstrate that dietary sodium intake is an important determinant of the renal and hormonal responses to neutral endopeptidase inhibition.

Adult↗
PubMed1995

Clearance of endogenous lithium in humans: altered dietary salt intake and comparison with exogenous lithium clearance.

We compared endogenous with exogenous lithium clearance (CLi) and studied the effects of dietary salt intake on endogenous CLi in healthy volunteers. Lithium was detectable within a narrow fourfold range in serum and in urine in all 25 subjects studied [serum (n = 25), mean 0.27 +/- 0.02 mumol/l, range 0.13-0.55 mumol/l; urine (n = 20), range 1.49-7.32, mean 4.09 +/- 0.36 mumol/24 h]. Mean clearance and fractional excretion of endogenous lithium were lower (15.2 +/- 2.0 ml/min and 16.4 +/- 2.1%, respectively) compared with results obtained using the exogenous CLi technique (25.5 +/- 1.7 ml/min and 27.9 +/- 2.1%; P < 0.01 and P < 0.05, respectively; n = 17). In a separate group of six normal subjects, absolute (8.7 +/- 2.9 vs. 20.7 +/- 3.8 ml/min) and fractional excretion of lithium (8.3 +/- 2.9 vs. 18.0 +/- 5.1%) were significantly lower on 5 days of low (31 +/- 10 mmol/day) vs. high sodium intake (357 +/- 78 mmol/day; P < 0.05). Use of endogenous CLi precludes the need for lithium tablets. This could be a particular advantage in population studies and permits serial measurement of CLi on different days. Our results show that it is important to take dietary sodium intake into account in studies of endogenous CLi. Lower values for endogenous compared with exogenous CLi could reflect differences in renal handling depending on the plasma lithium concentration. This clearly requires further study.

Diet, Sodium-Restricted↗
PubMed1995

Reduction of salt intake during converting enzyme inhibitor treatment compared with addition of a thiazide.

A moderate reduction in salt intake lowers blood pressure in individuals with hypertension and improves blood pressure control in those taking a converting enzyme inhibitor. However, it is unclear how effective reduction of salt intake is compared with addition of other drugs, in particular, thiazide diuretics. We directly compared the separate effects on blood pressure of reducing sodium intake or adding a thiazide diuretic in the pressure of a converting enzyme inhibitor in a double-blind, randomized, crossover study. We studied 11 subjects with essential hypertension who had been taking 25 mg captopril twice daily for at least 1 month. In the double-blind study, after 1 month of captopril alone, supine blood pressure was 151 +/- 5/95 +/- 4 (SEM) mm Hg. With the addition of 25 mg hydrochlorothiazide once daily for 1 month, blood pressure fell to 137 +/- 5/87 +/- 3 mm Hg. When a moderate reduction in salt intake (from 206 +/- 26 to 109 +/- 20 mmol urinary sodium/24 h) was added to captopril for 1 month, blood pressure was reduced by a similar amount (to 137 +/- 4/90 +/- 3 mm Hg). Plasma potassium fell during the diuretic treatment (3.9 +/- 0.1 to 3.7 +/- 0.1 mmol/L, P < .05) but increased nonsignificantly during salt reduction (3.9 +/- 0.1 to 4.1 +/- 0.2 mmol/L). These results clearly demonstrate that moderate salt reduction, which can be easily achieved, is as effective as a thiazide diuretic in lowering blood pressure in the presence of a converting enzyme inhibitor and has the particular advantage that plasma potassium does not decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

N-terminal atrial natriuretic peptide and atrial natriuretic peptide in human plasma: investigation of plasma levels and molecular circulating form(s) using radioimmunoassays for pro-atrial natriuretic peptide (31-67), pro-atrial natriuretic peptide (1-30) and atrial natriuretic peptide (99-126).

1. The aim of this study was to determine plasma levels of N-terminal atrial natriuretic peptide and atrial natriuretic peptide in normal subjects and in patients with essential hypertension, cardiac transplant and chronic renal failure, using radioimmunoassays directed towards the mid-portion pro-atrial natriuretic peptide (31-67) and pro-atrial natriuretic peptide (1-30) of the N-terminal atrial natriuretic peptide and atrial natriuretic peptide (99-126). The circulating form(s) of the immunoreactive N-terminal atrial natriuretic peptide in plasma extracts has been investigated using all three radioimmunoassays by means of gel filtration chromatography to further clarify the major immunoreactive molecular circulating form(s) of N-terminal atrial natriuretic peptide in man. 2. The plasma level (mean +/- SEM) of N-terminal pro-atrial natriuretic peptide (31-67) in the normal subjects was 547.2 +/- 32.7 pg/ml (n = 36) and was significantly elevated in patients with essential hypertension (730.2 +/- 72.3 pg/ml, P < 0.025, n = 39), in cardiac transplant recipients (3214.0 +/- 432.2 pg/ml, P < 0.001, n = 9) and in patients with chronic renal failure (3571.8 +/- 474.1 pg/ml, P < 0.001, n = 11). Plasma levels of N-terminal pro-atrial natriuretic peptide (1-30) and atrial natriuretic peptide were similarly elevated in the same patient groups when compared with the mean plasma values in the normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Evidence for a new role of natriuretic peptides: control of intraocular pressure.

To study the possible physiological role of atrial natriuretic peptide (ANP) in the regulation of intraocular pressure (IOP) the effects of an increase of endogenous ANP within the physiological range induced by the neutral endopeptidase 24.11 (NEP) inhibitor candoxatril were examined. In a single masked placebo controlled trial, seven patients were studied with normal IOP (six male, one female; average age 50 (range 37-62 years). Intraocular pressure in each eye was measured after 2 weeks of placebo, after 4 weeks of candoxatril 200 mg twice daily, and during the first 3 days of placebo washout. With 4 weeks of candoxatril, endogenous plasma ANP levels increased from 4.2 (SEM 1.5) to 6.0 (1.5) pmol/l (p < 0.04) and there was a significant decrease in mean arterial pressure from 119 (4) to 110 (3) mm Hg (p < 0.02; 12 hours after treatment). There was a significant reduction in IOP after 4 weeks' treatment with candoxatril (right eye 2.1 (0.8) mm Hg, p < 0.05 paired t test, left eye 2.8 (0.8) mm Hg, p < 0.02). The mean fall in IOP was 11% (4%) in the right eye and 16% (3%) in the left eye and the fall in IOP was greater the higher the initial IOP. The reduction in IOP with chronic NEP inhibition was positively correlated with the increase in ANP levels but not with changes in blood pressure. These findings suggest that ANP may play a physiological role in the regulation of IOP. As the fall in IOP was greater in subjects with higher initial IOP, NEP inhibitors may be of therapeutic value in the management of glaucoma.

Adult↗
PubMed1994

Angiotensin II suppression is a major factor permitting excretion of an acute sodium load in humans.

We examined the role of circulating angiotensin II (ANG II) in the excretion of an acute Na+ load in eight healthy subjects given 2 liters 0.9% saline in a placebo-controlled crossover study. On the control day, plasma ANG II decreased to 40-60% of basal values and 35 +/- 9 (SE) mmol of Na+ was excreted in the 5 h after the start of saline infusion. When ANG II was infused to maintain plasma ANG II levels at around basal values (6.6 +/- 1.6 pmol/l), only 7 +/- 8 mmol of Na+ was excreted in the same period (P < 0.05). In a previous similar study in which the fall in aldosterone was prevented by infusion of aldosterone, 16 +/- 16 mmol of Na+ was excreted vs. 36 +/- 16 mmol on the control day in comparable 5-h periods. Suppression of ANG II is one of the major factors permitting the acute increase in Na+ excretion after an intravenous Na+ load. ANG II has direct actions on Na+ excretion in addition to its effects on aldosterone.

Adult↗