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Introduction: The sodium-hydrogen exchanger (NHE) is integral to the processes that facilitate cell growth and may contribute to the development of left ventricular hypertrophy. The aim of this study was to examine the relationship between platelet sodium-hydrogen exchanger activity and left ventricular mass index (LVMI). Methods: Twenty male untreated Caucasians (mean age ± s.d.: 48 ± 13; body mass index: 29 ± 4 kg/m[SUP2]) with a wide range of blood pressures were studied (mean BP: 152 ± 22/93 ± 15 mm Hg; range: 115-190/61-117 mm Hg). Sodium-hydrogen exchanger activity was determined as the rate of sodium-dependent recovery of intracellular pH in isolated platelets loaded with BCECF and acidified to pH 6.25 using nigericin. LVMI was calculated from measurements made by M-mode echocardiography. Associations between continuous variables were examined using parametric tests. Results: The mean rate of pHi recovery was 0.15 ± 0.03 dpHi/s (range: 0.09-0.21). Mean LVMI was 120 ± 32 g/m[SUP2] (range: 56-178) and was not significantly correlated with either systolic (r = 0.39, P = 0.09) or diastolic blood pressure (r = 0.27, P = 0.3). Platelet NHE activity was not significantly correlated with LVMI (r = 0.06; P = 0.8). Platelet NHE activity was not significantly different between subjects with (n = 7 with LVMI > 131 g/m[SUP2]) and without left ventricular hypertrophy (n = 13). Conclusions: The results of this study show that platelet NHE activity is not significantly correlated with LVMI. These data contrast with previously described correlations of LVMI with exchanger activity measured in leucocytes and erythrocytes; and indicate that the relationship between LVMI and exchanger activity may be specific to the cell type in which exchanger activity is measured. [ABSTRACT FROM AUTHOR]

Polymorphisms of the epithelial sodium channel may raise blood pressure by increasing renal sodium reabsorption. This study examines frequency distributions and associations with hypertension of the T594M and of the G442V polymorphisms of the β subunit of the epithelial sodium channel in a population-based sample. We studied a stratified random sample of 459 subjects (279 women), aged 40-59 years, of black African origin from general practices' lists within a defined area of South London. All were first generation immigrants. The polymorphic variants were detected using single strand conformational polymorphism technique (SSCP). The prevalence of hypertension (BP ⩾160 and/or 95 mm Hg or on drug therapy) was 43%; of these, 76% were on drug therapy. The main analysis was carried out by three ordered blood pressure categories (I to III) according to increasing blood pressure and presence or absence of drug therapy. The frequency of the 594M variant (heterozygotes and homozygotes) was 4.6%; the frequency of the 442V variant was higher (27.0%). The frequency of the 594M variant increased with increasing blood pressure category (P = 0.05) and was more common in hypertensives than normotensives. By contrast the frequency of the 442V variant did not vary across increasing blood pressure categories (P = 0.62). No gender difference was observed. Adjustment for age, sex and body mass index did not alter these findings. These results suggest that the 594M variant may contribute to high blood pressure in black people of African origin whereas the G442V polymorphism is unlikely to influence blood pressure in this population. [ABSTRACT FROM AUTHOR]

Abnormalities in acid-base regulation have previously been reported both in hypertensive humans and animals and a link between abnormalities in renal sodium handling and acid excretion may be particularly important in black hypertensives. The objectives of this study were to compare indices of urinary acid excretion (urinary pH, ammonium and titratable acid excretion) between normotensives and hypertensive people of African origin. Measurements were carried out in 86 black individuals of African origin in a case-control design (19 normotensive; 67 hypertensive). Of these, 17 normotensive and 17 patients with essential hypertension were matched for age, sex and weight. Group comparisons were carried out by unpaired t-tests or two-way analysis of variance and group values are given as means ± s.d. Urinary pH was significantly higher in the hypertensives both in the unmatched groups and in the matched groups. In the 17 matched pairs: urinary pH in the hypertensive individuals was 6.36 ± 0.54 and 5.84 ± 0.53 in the normotensives, respectively; P = 0.007. Additionally, urinary titratable acidity was significantly lower in the hypertensives than in the normotensives (25.4 ± 13.7 vs 16.7 ± 10.7 mmol/24 h; P = 0.047) but there were no significant differences in urinary ammonium excretion. The mechanisms for the apparent reduction in acid excretion in the hypertensives is not clear but these results highlight the possibility that hypertension in blacks is associated with abnormalities of renal sodium and hydrogen exchange with compensatory increases in renal ammonium production. [ABSTRACT FROM AUTHOR]

• Use non-pharmacological measures in all hypertensive and borderline hypertensive people. • Initiate antihypertensive drug therapy in people with sustained systolic blood pressures (BP) &ges;160 mm Hg or sustained diastolic BP &ges;100 mm Hg. • Decide on treatment in people with sustained systolic BP between 140 and 159 mm Hg or sustained diastolic BP between 90 and 99 mm Hg according to the presence or absence of target organ damage, cardiovascular disease or a 10-year coronary heart disease (CHD) risk of &ges;15% according to the Joint British Societies CHD risk assessment programme/risk chart. • In people with diabetes mellitus, initiate antihypertensive drug therapy if systolic BP is sustained &ges;140 mm Hg or diastolic BP is sustained &ges;90 mm Hg. • In non-diabetic hypertensive people, optimal BP treatment targets are: systolic BP <140 mm Hg and diastolic BP <85 mm Hg. The minimum acceptable level of control (Audit Standard) recommended is <150/<90 mm Hg. Despite best practice, these levels will be difficult to achieve in some hypertensive people. • In diabetic hypertensive people, optimal BP targets are; systolic BP <140 mm Hg and diastolic BP <80 mm Hg. The minimum acceptable level of control (Audit Standard) recommended is <140/<90 mm Hg. Despite best practice, these levels will be difficult to achieve in some people with diabetes and hypertension. • In the absence of contraindications or compelling indications for other antihypertensive agents, low dose thiazide diuretics or beta-blockers are preferred as first-line therapy for the majority of hypertensive people. In the absence of compelling indications for beta-blockade, diuretics or long acting dihydropyridine calcium antagonists are preferred to beta-blockers in older subjects. Compelling indications and contra-indications for all antihypertensive drug classes are specified. • For most hypertensives, a combination of antihypertensive drugs will be... [ABSTRACT FROM AUTHOR]

Focuses on problems associated with using Fura-2 to measure free intracellular calcium concentrations in human red blood cells. Introduction of Fura-2; Influence of high concentration of haemoglobin on the properties of Fura-2; Measurement of the excitation spectra of Fura-2 and red blood cell using Fura-2.

High blood pressure is the most important risk factor for cardiovascular disease. With the information on systolic blood pressure from the recently published meta-analysis of prospective studies, we calculated the reductions in stroke and ischaemic heart disease with control of all hypertensives to a systolic blood pressure of 140 mmHg. For adults there would be a reduction of 28-44% in stroke and 20-35% in ischaemic heart disease depending on age. In the UK, this would prevent approximately 21 400 stroke deaths and 41 400 ischaemic heart disease deaths each year. Around half of those who suffer a stroke or ischaemic heart disease survive, there would be a proportionate decrease in these people as well. These amount to approximately 42 800 strokes and 82 800 ischaemic heart diseases saved, making a total of 125 600 events saved a year in the UK. This would result in a reduction in disability and major cost savings both to individuals, their families and the Health Service. The blood pressure levels and control of blood pressure in many countries are similar to those in the UK, so the reductions in stroke and ischaemic heart disease worldwide, if the same control of high blood pressure could be obtained, would be immense. [ABSTRACT FROM AUTHOR]

Focuses on the regression of atherosclerotic renal artery stenosis with aggressive lipid lowering therapy in patients with coronary heart disease. Explanation of lipid lowering therapy; Risk factors associated with atherosclerotic renal artery stenosis.

Focuses on dihydropryidine calcium channel blockers and its side effect on peripheral oedema. Causes of peripheral oedema; Treatment of mild oedema; Incidence of oedema in younger patients and older patients.

Discusses the occurrence of gingival hyperplasia due to calcium channel blockers with reference to a case study in Great Britain. Highlights of the case of a middle-aged patient with a history of hypertension and hypercholesterolaemia; Key observations related to the occurrence of gingival overgrowth; Process of the growth of gingival hyperplasia.

Aims: Previous studies have reported tight linkage disequilibrium between the T235 and the A(-6) molecular variants of the angiotensinogen gene. This study was designed primarily to ascertain whether a similar relationship exists between the M235 and the G(-6) variants of the gene. We have investigated the degree of agreement between the genotypes of the M235T and the G(-6)A polymorphisms in two ethnic groups. Methods: Subjects were an heterogeneous group of normotensive and hypertensive subjects of Caucasian (n = 77) and Afro-Caribbean (n = 51) origin. DNA was extracted from whole blood and was genotyped for both the M235T and G(-6)A polymorphisms using PCR-based methods. Results: The distribution frequencies of the MM, MT, and TT genotypes were 0.39, 0.42, and 0.20 in white subjects, and 0.09, 0.17, and 0.74 in black subjects, respectively (chi-square, P < 0.0001). The distribution of AA, GA, and GG genotypes also differed between the two groups as follows: 0.22, 0.48, and 0.30 in white subjects, and 0.82 and 0.18 and 0 in black subjects respectively (chi-square, P < 0.0001). The agreement for TT-AA, MT-GA, and MM-GG was 93%, 91%, and 76% respectively in white and 100%, 67% and 0% respectively in black subjects. Conclusions: The results indicate ethnic differences in the distribution of both M235T and G(-6)A genotypes. The trend towards a decrease in the degree of agreement in the order of TT-AA > MT-GA > MM-GG suggests that linkage disequilibrium between the M235 and G-6 variant does not mirror that observed with the T235 and A-6 variants. These observations may have significant implications regarding the associations between the G(-6)A polymorphism and hypertension. However, this needs to be further investigated. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor on the treatment of hypertension published in the November 1999 issue of the medical journal 'Journal of Human Hypertension.' Diagnosis of hypertension with an angiotensin converting enzyme; Effects of the drug, losartan on patients with hypertension.

Focuses on the determination of aneurysmal aortoiliac disease and severe proximal renal artery stenosis in a patient with a history of acute myocardinal infarction, using digital aortography. Cause of secondary hypertension and chronic renal failure; Effect of the increase of severity of peripheral vascular disease on renal artery stenosis; Requirement of renal artery disease patients to undergo angioplasty.

Focuses on the diagnosis of secondary hypertension. Role of clinical genetics in the diagnosis; Measurement of blood pressure in a genetic clinic; Description of case study of a patient diagnosed with hypertension.

Examines the association between nitric oxide (NO) activity and essential hypertension. Reason for the use of plasma and urinary nitrate as an index of endogenous NO; Measurement of urinary and plasma nitrate; Comparison of normotensive and hypertensive people.

Polymorphisms of the epithelial sodium channel may raise blood pressure by increasing renal sodium reabsorption. This study examines frequency distributions and associations with hypertension of the T594M and of the G442V polymorphisms of the beta subunit of the epithelial sodium channel in a population-based sample. We studied a stratified random sample of 459 subjects (279 women), aged 40-59 years, of black African origin from general practices' lists within a defined area of South London. All were first generation immigrants. The polymorphic variants were detected using single strand conformational polymorphism technique (SSCP). The prevalence of hypertension (BP > or =160 and/or 95 mm Hg or on drug therapy) was 43%; of these, 76% were on drug therapy. The main analysis was carried out by three ordered blood pressure categories (I to III) according to increasing blood pressure and presence or absence of drug therapy. The frequency of the 594M variant (heterozygotes and homozygotes) was 4.6%; the frequency of the 442V variant was higher (27.0%). The frequency of the 594M variant increased with increasing blood pressure category (P = 0.05) and was more common in hypertensives than normotensives. By contrast the frequency of the 442V variant did not vary across increasing blood pressure categories (P = 0.62). No gender difference was observed. Adjustment for age, sex and body mass index did not alter these findings. These results suggest that the 594M variant may contribute to high blood pressure in black people of African origin whereas the G442V polymorphism is unlikely to influence blood pressure in this population.

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.

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.

Increasing evidence from animal, epidemiological, intervention studies and treatment trials all clearly point to the important role that salt intake plays in determining blood pressure (BP). Of more current interest is whether salt may have other deleterious effects independent of its role in high BP. For instance, salt intake plays an important role in left ventricular hypertrophy independent of its effect on BP. Experimental evidence and some epidemiological evidence also suggest that salt intake may have an adverse effect on stroke mortality which may be independent of its effect on BP. In animal models of renal failure, dietary salt restriction has been found to slow the progression of the renal impairment, but no studies as yet have been reported in humans. Salt intake has also been associated with asthma, stomach and nasopharyngeal cancer. Increasing salt intake produces changes in the chemical composition of urine, particularly an increase in calcium excretion which will predispose to kidney stone formation and has also been shown to increase hydroxyproline excretion indicating increased bone resorption. It is likely that a high salt intake may be one of several factors aggravating osteoporosis. This may be particularly relevant in patients with essential hypertension who already have an increased urinary calcium excretion and may in the long term be at greater risk of osteoporosis. Restriction of salt intake reduces urinary calcium excretion and, perhaps, like thiazide diuretics may be beneficial in the long-term prevention of bone demineralisation.

Although it is generally assumed that small arteries are truly isometric when studied in a myograph, these arteries significantly shorten during the normalisation procedure. We assessed the effects of this shortening on calculation of morphological variables in small arteries using vessel length before and after normalisation. Subcutaneous resistance arteries were dissected from gluteal biopsies obtained from normotensive subjects (n = 7, supine pressure 116/69 +/- 5/3(SE) mmHg, internal artery diameter 276 +/- 16 microM) and patients with essential hypertension on no treatment (n = 13, supine pressure 160/102 +/- 4/2 mmHg, internal diameter 256 +/- 9 microM) mounted on a small vessel myograph. Using the actual shortened 'normalised' length compared with measurement using the original artery length, media thickness was significantly greater both in normal subjects (24.0 +/- 2.7 microM vs. 22.7 +/- 2.7 microM, 2 P < 0.05, paired t-test) and in hypertensives (27.6 +/- 1.5 microM vs. 26.5 +/- 1.4 microM, 2 P < 0.001). Calculated from the actual shortened 'normalised' length vs. original artery length, media:lumen ratio was also increased in the normal subjects (8.6 +/- 0.6 vs. 8.2 +/- 0.6 2 P < 0.05) and in the hypertensives (11.2 +/- 0.7 vs. 10.7 +/- 0.7, 2 P < 0.001). For the media thickness in normal subjects this was an increase of 6% (95% CI: 1-12%) and in hypertensives of 4% (95% CI: 2-6%). Standard methods for study of small arteries underestimate media thickness and media:lumen ratio in normal subjects and in hypertensives.(ABSTRACT TRUNCATED AT 250 WORDS)

We describe angiotensinogen gene (AGT) polymorphic frequencies in different ethnic groups in London, both normotensive and hypertensive. The methodology is a recently described direct PCR technique. Results show that there is a marked difference in T-235 frequency between ethnic groups. However, there was no apparent association of T-235 with hypertension.

Platelet size, a determinant of platelet function, is a newly emerging risk factor for atherothrombosis. Platelet volume has previously been shown, using less than ideal methodology, to be increased in essential hypertension. Mean platelet volume was measured in 38 patients with essential hypertension and 38 paired normotensive control subjects matched for age and sex. Platelet volume, median (interquartile ranges) 7.7 (7.2-8.5) fl vs. 7.8 (7.5-8.4) fl (2P = 0.40), platelet count 242 (220-288) x 10(9)/l vs. 243 (215-292) x 10(9)/l (2P = 0.68) and platelet mass 1.91 (1.67-2.18) ml/l vs. 1.84 (1.70-2.23) ml/l (2P = 0.90) were similar in the hypertensive patients (supine BP: SBP 168 (153-178) mmHg, DBP 103 (98-110) mmHg) and control subjects (SBP 126 (112-138) mmHg, DBP 78 (74-82) mmHg). Serum lipids and plasma glucose and creatinine concentrations were not different between the groups. Mean BP did not correlate with platelet volume (rs = -0.100, 2P = 0.39) or platelet count (rs = 0.111, 2P = 0.34). These data suggest that platelet volume is not altered in essential hypertension.

Nineteen patients with essential hypertension on regular treatment with nifedipine tablets 20 mg twice daily and whose DBP was < 95 mmHg on at least two occasions two weeks apart were entered in a double-blind randomised crossover study of three weeks treatment with nifedipine coat core (new formulation) either as 30 mg one daily or as 60 mg once daily dose. BP and plasma nifedipine levels were measured at 24, two, four and six hours after dosing. The pattern of BP response to both doses was similar over the 24h period. However, a greater BP lowering effect was achieved with 60 mg compared with 30 mg. The BP lowering effect of both doses was less at 24h after the last dose compared with peak effect. Plasma nifedipine levels were significantly associated with the BP lowering effect in the group as a whole (i.e. the higher the nifedipine levels, the lower the BP) and were significantly less at 24 hours compared with peak. Nifedipine in the coat core formulation is effective in lowering BP in patients with essential hypertension. The 60 mg dose is more effective than the 30 mg dose and induces higher nifedipine levels which are associated with greater BP lowering effect. However, the maximum BP lowering effect is not maintained up to 24 hours.

The objective of this study was to investigate the relationships between erythrocyte Na-Li countertransport, plasma renin activity (PRA), plasma aldosterone and plasma atrial natriuretic peptide (ANP) in a population-based study, in a cross-sectional observation of a randomly selected sample of a male working population, conducted at the Medical Care Center at the Olivetti Factory in Pozzuoli (Naples). One hundred and seventy-nine male employees aged 45.3 +/- 6.8 years (mean +/- SD), all on unrestricted diet and on no pharmacological treatment were studied. Statistical associations between Na-Li countertransport activity and the hormonal factors being studied were investigated, with control for the possible confounding effects of age, BP and sodium intake. Na-Li countertransport was significantly and positively associated with plasma aldosterone concentration (r = 0.228, P < 0.01) but not with PRA or plasma ANP. Men in the highest quartile of the Na-Li countertransport distribution had significantly higher plasma aldosterone levels than men in the other quartiles (P < 0.01) and this difference was independent of age, body mass, PRA, urinary sodium excretion and blood pressure. It is concluded that plasma aldosterone levels are enhanced and disproportionately high relative to plasma renin activity in individuals with high Na-Li countertransport, independently of known potential confounders.

Nifedipine is an effective compound for the treatment of hypertension. However, even as a tablet formulation it is relatively short acting requiring two or three times daily administration. Amlodipine is a long-acting calcium antagonist and effectively lowers BP in patients with essential hypertension. In the present study we compared the BP-lowering effect of nifedipine and amlodipine in patients with essential hypertension. Thirteen patients were studied. They had been on nifedipine tablets for at least four weeks and DBP had been consistently > 95 mmHg. After a further month run-in on nifedipine they entered a randomised double-blind crossover study of one month' treatment with either nifedipine tablet (20 mg twice daily) or amlodipine (5 mg once daily). BP was measured 12 and 2 hours after the last dose of nifedipine and 24 and 2 hours after the last dose of amlodipine. There was a significant peak/trough effect while on nifedipine tablets, the BP being significantly higher at 12 hours than at 2 hours after the last dose (155.2/90.9 +/- 4.6/1.7 vs. 136.1/84.8 +/- 4.3/1.7 mmHg; P < 0.001/P < 0.005). There was no overall difference in BP between nifedipine and amlodipine treatment when BPs were taken at the respective troughs (i.e. 12 hours and 24 hours). If anything, amlodipine tended to be slightly more effective at least on supine SBP (155.2/90.9 +/- 4.6/1.7 vs. 147.6/89.1 +2- 4.3/1.8 mmHg; P < 0.05, NS). In conclusion, amlodipine given once daily is at least as effective as nifedipine tablets given twice daily in patients with essential hypertension.

We have developed a radioimmunoassay for the measurement of immunoreactive BNP (1-32) in human plasma. Simultaneous measurement of ANP have also been carried out to allow for direct comparison between circulating BNP and ANP. Plasma levels of immunoreactive BNP (means +/- SEM) were 1.1 +/- 0.1 pmol/l in 36 normal healthy subjects and were significantly elevated in 50 patients with essential hypertension (1.6 +/- 0.2 pmol/l, P < 0.02). Similarly, in patients with essential hypertension plasma levels of ANP were also significantly raised (5.5 +/- 0.6 pmol/l, P < 0.001) when compared with the group of normal healthy subjects (2.8 +/- 0.2 pmol/l). ANP was significantly higher than BNP in normal subjects and in patients with essential hypertension, with ANP/BNP ratios of 2.8 +/- 0.2 and 3.8 +/- 0.3, respectively, in these two groups. A major finding was a significant and positive association between plasma levels of both BNP and ANP within the healthy subjects (r = 0.49, P < 0.05, n = 36) and within the hypertensive subjects (r = 0.76, P < 0.001, n = 50). When all plasma values for BNP and ANP were taken together for both groups, there was an overall correlation coefficient of 0.65 (P < 0.001, n = 86). Both BNP and ANP had significant positive associations with age in hypertensive patients, with correlation coefficients of 0.53 (P < 0.001, n = 50) and of 0.53 (P < 0.001, n = 50) for BNP and ANP, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)