Effect of air pollutants on ambulatory blood pressure.

BACKGROUND AND METHODOLOGY: Air pollutants have a significant impact on public health. The aim of the study was to find out the relationship between ambulatory blood pressure measured by 24-h ambulatory blood pressure monitoring (ABPM) and the atmospheric pollutants that are measured regularly (PM10, PM2.5, NO2 and SO2). An observational study of temporal and geographic measurements of individual patients (case-time series design) was carried out in Primary Care Centres and Hypertension Units in the Barcelona metropolitan area. We included 2888 hypertensive patients≥18 years old, untreated, with a first valid ABPM performed between 2005 and 2014 and with at least one air pollution station within a radius of <3km. RESULTS AND CONCLUSIONS: The mean age was 54.3 (SD 14.6) years. 50.1% were women and 16.9% of the sample were smokers. Mean 24-h blood pressure (BP) was 128.0 (12.7)/77.4 (9.7) mmHg. After adjusting for mean ambient temperature and different risk factors, a significant association was found between ambulatory diastolic BP (DBP) and PM10 concentrations the day before ABPM. For each increase of 10µg/m3 of PM10, an increase of 1.37mmHg 24-h DBP and 1.48mmHg daytime DBP was observed. No relationship was found between PM2.5, NO2 and SO2 and ambulatory BP, nor between any pollutant and clinical BP. The concentration of PM10 the day before the ABPM is significantly associated with an increase in 24-h DBP and daytime DBP.

[Determination of urinary albumin excretion in arterial hypertension]. / Determinación de la excreción urinaria de albúmina en la hipertensión arterial.

BACKGROUND AND AIM: Urinary albumin excretion (UAE) measurement is recommended in the diagnosis and follow-up of the hypertensive patient. The aim of the study was to evaluate the proportion of hypertensives attended in Primary Care who had an evaluation of UAE in the last year, along with the methodology of the measurement. PATIENTS AND METHODS: A total of 958 investigators consecutively recruited 4786 hypertensives (first five patients who attended). When present, the measurement of UAE during the last year was obtained from clinical records. In those having this measurement, the type of urine collection (24hours, nighttime or morning spot), as well as the value and units of measure (mg/24h, µg/min, mg/g or mg/L) were recorded. RESULTS: Mean age was 66 years. 51% were men and 49% women. UAE was determined in 2301 patients (48.1%). In 329, 24-hour urine was collected, nighttime urine in 122 and in 1850 the collection came from a morning spot sample. However, only 696 patients from the latter group had the value of albumin corrected by the creatinine excretion. Thus, only 24% of hypertensive patients had a valid UAE measurement (mg/24h, µg/min or mg/g). Prevalence of microalbuminuria was 36%. The UAE determination was associated with older age, obesity, diabetes and better blood pressure control rates. CONCLUSION: Only half of hypertensive patients have a UAE measurement and in only 1 out of 4 a validated methodology has been used. It seems necessary a reinforcement of the messages contained in guidelines, as well as its applicability to any particular setting in order to promote a generalized and correct evaluation of UAE in hypertension.

[2022 Practice guidelines for the management of arterial hypertension of the Spanish Society of Hypertension]. / Guía práctica sobre el diagnóstico y tratamiento de la hipertensión arterial en España, 2022. Sociedad Española de Hipertensión - Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA).

Hypertension is the most important risk factor for global disease burden. Detection and management of hypertension are considered as key issues for individual and public health, as adequate control of blood pressure levels markedly reduces morbidity and mortality associated with hypertension. Aims of these practice guidelines for the management of arterial hypertension of the Spanish Society of Hypertension include offering simplified schemes for diagnosis and treatment for daily practice, and strategies for public health promotion. The Spanish Society of Hypertension assumes the 2018 European guidelines for management of arterial hypertension developed by the European Society of Cardiology and the European Society of Hypertension, although relevant aspects of the 2017 American College of Cardiology/American Heart Association guidelines and the 2020 International Society of Hypertension guidelines are also commented. Hypertension is defined as a persistent elevation in office systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg, and assessment of out-of-office blood pressure and global cardiovascular risk are considered of key importance for evaluation and management of hypertensive patients. The target for treated blood pressure should be < 130/80 for most patients. The treatment of hypertension involves lifestyle interventions and drug therapy. Most people with hypertension need more than one antihypertensive drug for adequate control, so initial therapy with two drugs, and single pill combinations are recommended for a wide majority of hypertensive patients.

[Prevention of progression and regression of target organ damage. Future strategies]. / Prevención de la progresión y regresión de la lesión orgánica. Estrategias de futuro.

Treatment with renin-angiotensin system blockers (angiotensin converting-enzyme inhibitors and AT1 receptor antagonists) has shown clear benefits in distinct stages of cardiovascular disease (CVD). This treatment lowers blood pressure and prevents the appearance of markers of subclinical disease such as microalbuminuria, reduces cardiovascular and renal episodes in patients with subclinical lesions and prolongs survival in patients with clinical disease or organ dysfunction. Despite this unquestionable benefit, the residual risk in patients receiving these treatments often continues to be highly elevated and consequently strategies to reduce this risk are required. The present article reviews the options that may help to reduce cardiovascular disease. In addition to renin-angiotensin system blockers, these treatments include primary prevention in healthy individuals, stricter therapeutic goals, comprehensive risk control, more complete blocking of the renin-angiotensin system and the use of drugs with synergistic protective mechanisms.

Study of arterial stiffness in patients with an acute coronary event and chronic obstructive pulmonary disease confirmed by spirometry. / Estudio de la rigidez arterial en pacientes con un evento coronario agudo y enfermedad pulmonar obstructiva crónica confirmada por espirometría.

BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) worsens the prognosis for patients with an acute coronary event (ACE) treated with percutaneous coronary intervention. Objective To assess the effect of COPD on arterial stiffness in patients with an ACE. METHODS: The study included patients with an ACE treated with percutaneous coronary intervention. At 1 month, postbronchodilation spirometry was performed, and arterial stiffness and markers of myocardial damage (troponin T and ProBNP) were measured. RESULTS: We included 68 patients, 33% of whom had COPD (59% undiagnosed). The patients with COPD presented higher arterial stiffness values after adjusting for age and blood pressure readings. The troponin T and ProBNP levels were higher in the patients with COPD. CONCLUSIONS: Arterial stiffness is greater in patients with an ACE if they have concomitant COPD. These findings can help explain the poorer prognosis of patients with both conditions.

[Position statement on ambulatory blood pressure monitoring (ABPM) by the Spanish Society of Hypertension (2019)]. / Documento de la Sociedad Española de Hipertensión-Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA) sobre monitorización ambulatoria de la presión arterial (MAPA) 2019.

Conventional blood pressure (BP) measurement in clinical practice is the most used procedure for the diagnosis and treatment of hypertension (HT), but is subject to considerable inaccuracies due to, on the one hand, the inherent variability of the BP itself and, on the other hand biases arising from the measurement technique and conditions, Some studies have demonstrated the prognosis superiority in the development of cardiovascular disease using ambulatory blood pressure monitoring (ABPM). It can also detect "white coat" hypertension, avoiding over-diagnosis and over-treatment in many cases, as well detecting of masked hypertension, avoiding under-detection and under-treatment. ABPM is recognised in the diagnosis and management of HT in most of international guidelines on hypertension. The present document, taking the recommendations of the European Society of Hypertension as a reference, aims to review the more recent evidence on ABPM, and to serve as guidelines for health professionals in their clinical practice and to encourage ABPM use in the diagnosis and follow-up of hypertensive subjects. Requirements, procedure, and clinical indications for using ABPM are provided. An analysis is also made of the main contributions of ABPM in the diagnosis of "white coat" and masked HT phenotypes, short term BP variability patterns, its use in high risk and resistant hypertension, as well as its the role in special population groups like children, pregnancy and elderly. Finally, some aspects about the current situation of the Spanish ABPM Registry and future perspectives in research and potential ABPM generalisation in clinical practice are also discussed.

Chronic hypotension in hemodialysis patients: role of functional vascular changes and vasodilator agents.

AIMS: The aim of this study was to evaluate the hemodynamic pattern, vascular compliance, as well as the levels of vasoregulatory hormones and markers of inflammation and oxidative stress in a group of chronic hypotensive (CH) patients undergoing hemodialysis (HD) and to compare them with a group of normotensive HD patients. MATERIAL AND METHODS: 14 normotensive and 10 CH hemodialysis patients were included in the study. Hemodynamic characteristics were evaluated by means of the pulse waveform analysis. Plasma levels of nitrites, interleukin-6 (IL-6), malondialdehyde (MDA), PTH-related peptide (PTHrp), catecholamines, angiotensin II and endothelin were measured. RESULTS: Blood pressure (BP) and peripheral vascular resistances (PVR) were lower in the hypotensive group (p < 0.001 and p = 0.005, respectively), whereas cardiac output was similar in both groups. Large (C1) (p = 0.001) and small (C2) (p = 0.022) artery elasticity indices were higher in hypotensive patients. In the whole group, C1 and C2 inversely correlated with mean BP (MBP). Plasma levels of nitrites (p = 0.011) were higher in hypotensive patients and inversely correlated with MBP (r = -0.516, p = 0.012). Time on HD correlated with plasma nitrites (r = 0.478, p = 0.024) and inversely with MBP (r = -0.598, p = 0.003). CONCLUSIONS: CH in HD patients is characterized by decreased PVR, a preserved cardiac output and greater vascular compliance. CH is associated with longer time on HD and higher plasma levels of nitrites/nitrates, suggesting that an enhanced production of nitric oxide induced by long-term HD, could be involved in CH. These findings suggest that functional vascular changes, likely related to an enhanced production of vasodilator agents, are responsible for CH in HD patients.

[Spanish Society of Hypertension position statement on the 2017 ACC/AHA hypertension guidelines]. / Documento de la Sociedad Española de Hipertensión-Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA) sobre las guías ACC/AHA 2017 de hipertensión arterial.

The American College of Cardiology (ACC) and the American Heart Association (AHA) have recently published their guidelines for the prevention, detection, evaluation, and management of hypertension in adults. The most controversial issue is the classification threshold at 130/80mmHg, which will allow a large number of patients to be diagnosed as hypertensive who were previously considered normotensive. Blood pressure (BP) is considered normal (<120mmHg systolic and <80mmHg diastolic), elevated (120-129 and <80mmHg), stage 1 (130-139 or 80-89mmHg), and stage 2 (≥140 or ≥90mmHg). Out-of-office BP measurements are recommended to confirm the diagnosis of hypertension and for titration of BP-lowering medication. In management, cardiovascular risk would be determinant since those with grade 1 hypertension and an estimated 10-year risk of atherosclerotic cardiovascular disease ≥10%, and those with cardiovascular disease, chronic kidney disease and/or diabetes will require pharmacological treatment, the rest being susceptible to non-pharmacological treatment up to the 140/90mmHg threshold. These recommendations would allow patients with level 1 hypertension and high atherosclerotic cardiovascular disease to benefit from pharmacological therapies and all patients could also benefit from improved non-pharmacological therapies. However, this approach should be cautious because inadequate BP measurement and/or lack of systematic atherosclerotic cardiovascular disease calculation could lead to overestimation in diagnosing hypertension and to overtreatment. Guidelines are recommendations, not impositions, and the management of hypertension should be individualized, based on clinical decisions, preferences of the patients, and an adequate balance between benefits and risks.

[Ambulatory blood pressure monitoring is a useful tool for all patients]. / La monitorización ambulatoria de la presión arterial es un instrumento aconsejable para todos los pacientes.

Clinical blood pressure measurement (BP) is an occasional and imperfect way of estimating this biological variable. Ambulatory blood pressure monitoring (ABPM) is by far the best clinical tool for measuring an individual's blood pressure. Mean values over 24h, through the daytime and at night all make it more possible to predict organic damage and the future development of the disorder. ABPM enables the detection of white-coat hypertension and masked hypertension in both the diagnosis and follow-up of treated patients. Although some of the advantages of ABPM can be reproduced by more automated measurement without the presence of an observer in the clinic or self-measurement at home, there are some other elements of great interest that are unique to ABPM, such as seeing what happens to a patient's BP at night, the night time dipping pattern and short-term variability, all of which relate equally to the patient's prognosis. There is no scientific or clinical justification for denying these advantages, and ABPM should form part of the evaluation and follow-up of practically all hypertensive patients. Rather than continuing unhelpful discussions as to its availability and acceptability, we should concentrate our efforts on ensuring its universal availability and clearly explaining its advantages to both doctors and patients.

Modification over time of pulse wave velocity parallel to changes in aortic BP, as well as in 24-h ambulatory brachial BP.

Arterial stiffness as assessed by carotid-femoral pulse wave velocity (cfPWV) is a marker of preclinical organ damage and a predictor of cardiovascular outcomes, independently of blood pressure (BP). However, limited evidence exists on the association between long-term variation (Δ) on aortic BP (aoBP) and ΔcfPWV. We aimed to evaluate the relationship of ΔBP with ΔcfPWV over time, as assessed by office and 24-h ambulatory peripheral BP, and aoBP. AoBP and cfPWV were evaluated in 209 hypertensive patients with either diabetes or metabolic syndrome by applanation tonometry (Sphygmocor) at baseline(b) and at 12 months of follow-up(fu). Peripheral BP was also determined by using validated oscillometric devices (office(o)-BP) and on an outpatient basis by using a validated (Spacelabs-90207) device (24-h ambulatory BP). ΔcfPWV over time was calculated as follows: ΔcfPWV=[(cfPWVfu-cfPWVb)/cfPWVb] × 100. ΔBP over time resulted from the same formula applied to BP values obtained with the three different measurement techniques. Correlations (Spearman 'Rho') between ΔBP and ΔcfPWV were calculated. Mean age was 62 years, 39% were female and 80% had type 2 diabetes. Baseline office brachial BP (mm Hg) was 143±20/82±12. Follow-up (12 months later) office brachial BP (mm Hg) was 136±20/79±12. ΔcfPWV correlated with ΔoSBP (Rho=0.212; P=0.002), Δ24-h SBP (Rho=0.254; P<0.001), Δdaytime SBP (Rho=0.232; P=0.001), Δnighttime SBP (Rho=0.320; P<0.001) and ΔaoSBP (Rho=0.320; P<0.001). A multiple linear regression analysis included the following independent variables: ΔoSBP, Δ24-h SBP, Δdaytime SBP, Δnighttime SBP and ΔaoSBP. ΔcfPWV was independently associated with Δ24-h SBP (ß-coefficient=0.195; P=0.012) and ΔaoSBP (ß-coefficient= 0.185; P=0.018). We conclude that changes in both 24-h SBP and aoSBP more accurately reflect changes in arterial stiffness than do office BP measurements.

Oral calcium supplementation reduces intraplatelet free calcium concentration and insulin resistance in essential hypertensive patients.

We evaluated the effect of oral calcium supplementation on blood pressure, calcium metabolism, and insulin resistance in essential hypertension. After receiving a standard diet with 500 mg of calcium per day during a 4-week period, 20 nondiabetic, essential hypertensive patients were randomized in a double-blind fashion to receive oral calcium supplementation (1500 mg of calcium per day) or placebo for 8 weeks. At the end of the 4-week period of low-calcium diet and after the 8-week period of intervention, we measured blood pressure (by both office and 24-hour ambulatory blood pressure monitoring), calcium-regulating hormones [urinary hydroxyproline and serum osteocalcin, parathormone, and 1,25(OH)2-vitamin D3], intraplatelet free calcium concentration, fasting plasma glucose and insulin levels, and the insulin-sensitivity index (euglycemic-hyperinsulinemic clamp). Compared with patients maintained at low calcium intake, essential hypertensive patients under oral calcium supplementation significantly reduced serum osteocalcin (from 22.2 +/- 1.9 to 17.9 +/- 2.0 micrograms/L; P = .0015), parathormone (from 4.20 +/- 0.38 to 3.30 +/- 0.36 pmol/L; P = .0003), and 1,25(OH)2-vitamin D3 (from 98.0 +/- 11.0 to 61.6 +/- 5.7 pmol/L; P = .0062). Likewise, we found a significant reduction in intraplatelet free calcium concentration (from 35.9 +/- 1.2 to 26.5 +/- 0.8 nmol/L; P = .0005) and fasting plasma insulin levels (from 71.8 +/- 5.9 to 64.6 +/- 6.2 pmol/L; P = .05) and a significant increase in the insulin-sensitivity index (from 2.89 +/- 0.77 to 4.00 +/- 0.95 mg.kg-1.min-1; P = .0007). None of these parameters were significantly modified in patients maintained at low calcium intake. Office and 24-hour mean values of systolic and diastolic blood pressure did not change after 8 weeks of oral calcium supplementation or placebo.

Renin-angiotensin system genetic polymorphisms and salt sensitivity in essential hypertension.

We evaluated the association between salt-sensitive hypertension and 3 different genetic polymorphisms of the renin-angiotensin system. Fifty patients with essential hypertension were classified as salt sensitive or salt resistant, depending on the presence or absence of a significant increase (P<0.05) in 24-hour ambulatory mean blood pressure (BP) after high salt intake. The insertion/deletion (I/D) angiotensin-converting enzyme (ACE) gene, the M235T angiotensinogen (AGT) gene, and the A1166C angiotensin II type 1 (AT1) receptor gene polymorphisms were determined with the use of standard polymerase chain reaction methods. Twenty-four (48%) patients with significantly increased (P<0.05) 24-hour mean BP with high salt intake (from 107.3+/-9.4 to 114.8+/-10.6 mm Hg) were classified as salt sensitive. In the remaining 26 patients (52%), high salt intake did not significantly modify 24-hour mean BP (from 107.6+/-10 to 107. 8+/-9 mm Hg), and they were classified as having salt-resistant hypertension. We did not find any significant association between either M235T AGT or A1166C AT1 receptor genotypes and the BP response to high salt intake. However, patients with essential hypertension homozygous for the insertion allele of the ACE gene (II) had a significantly higher BP increase with high salt intake (9. 8+/-8.1 mm Hg for systolic BP and 5.2+/-4.2 mm Hg for diastolic BP) than that observed in patients homozygous for the deletion allele (DD) (1.2+/-5.9 mm Hg for systolic BP; P=0.0118 and -0.2+/-4.2 mm Hg for diastolic BP; P=0.0274). Heterozygous patients (ID) exhibited an intermediate response. The prevalence of salt-sensitive hypertension also was significantly higher (P=0.012) in II (67%) and DI patients (62%) compared with DD hypertensives (19%). We conclude that a significant association exists between the I/D polymorphism of the ACE gene and salt-sensitive hypertension. Patients with II and DI genotypes have significantly higher prevalence of salt sensitivity than DD hypertensives.

Increased activity of the Mg2+/Na+ exchanger in red blood cells from essential hypertensive patients.

Epidemiological, clinical, and experimental evidence suggests a relation between Mg2+ metabolism and essential hypertension. The aim of the present study was the detection of abnormalities of the erythrocyte Mg2+/Na+ exchanger in essential hypertensive patients. We studied 66 untreated essential hypertensive patients and 36 normotensive control subjects. Maximal efflux rates of total Mg2+ efflux and the Na(+)-dependent and Na(+)-independent components of Mg2+ efflux were determined in Mg(2+)-loaded red blood cells. Mg2+/Na+ exchanger was calculated as the Na(+)-dependent component of the Mg2+ efflux. Mean values of Mg2+/Na+ exchanger were clearly elevated in hypertensive subjects with respect to normotensive control subjects [184.7 +/- 15.7 versus 84.4 +/- 6 mumol(L.cell.h)-1; P < .001]. This elevation was due primarily to the increased total Mg2+ efflux [324.2 +/- 21.9 versus 257.9 +/- 17.3 mumol(L.cell.h)-1; P < .05], whereas the Na(+)-independent component was not significantly different between the groups [154.5 +/- 11.8 versus 173.4 +/- 15.5 mumol(L.cell.h)-1; P = NS]. Moreover, total erythrocyte Mg2+ content was slightly reduced in hypertensive patients with respect to normotensive control subjects (1.84 +/- 0.04 versus 2.07 +/- 0.04 mmol/L.cell; P < .001). Using the 99% confidence limits of the normotensive population as the normal range, 30 (45.5%) hypertensive subjects showed values of Mg2+/Na+ exchanger higher than 160 mumol(L.cell.h)-1. The Mg2+/Na+ exchanger was inversely correlated with basal intraerythrocyte Mg2+ content (r = -.323; P = .001). From a clinical point of view, we found a positive correlation between diastolic blood pressure values and Mg2+/Na+ exchanger (r = .246; P < .05) in the sample of essential hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

G-Protein beta(3) subunit gene variant and left ventricular hypertrophy in essential hypertension.

A functional genetic variant consisting of a C825T substitution in the GNB3 gene, encoding for the G-protein beta(3) subunit, has been associated with enhanced G-protein activation and cell growth. The aim of the study was to investigate the association of this polymorphism with left ventricular hypertrophy (LVH) in a sample of patients with essential hypertension. Left ventricular mass was assessed by 2-mode echocardiography in 86 patients with essential hypertension, and GNB3 C825T genotype was determined by polymerase chain reaction and restriction digestion. Thirty-seven (0.43) patients were homozygous for the C allele (CC), 40 (0.47) were heterozygous (CT), and 9 (0.10) were homozygous for the T allele (TT). The genotype distribution among the patients was in Hardy-Weinberg equilibrium. Values of left ventricular end-diastolic diameter (52.0+/-0.7 versus 48.9+/-0.9 mm, P=0.007), posterior wall thickness (11.3+/-0.2 versus 10.6+/-0.2 mm, P=0.042), and left ventricular mass index (152.7+/-4.4 versus 135.2+/-6.4 g/m(2), P=0. 023) were significantly higher in patients with CT and TT genotypes considered together (CT+TT) than in CC patients. The distribution of the genotypes was significantly different when comparing patients with LVH: 20 (0.33) CC and 40 (0.67) CT+TT patients had this complication, and 17 (0.65) CC and 9 (0.35) CT+TT patients did not (P<0.01). The frequency of the T allele was significantly different among patients with (0.40) and without (0.20) LVH (P<0.01). A logistic regression analysis showed that the association between the T allele and LVH was independent of age, mean blood pressure, body mass index, and alcohol consumption. The relative risk of LVH in patients bearing the T allele (CT+TT group) compared with CC hypertensive patients was 3.03 (95% CI 1.14 to 8.05). The findings suggest an association between LVH and the 825T allele in hypertensive patients.

Effect of alcohol abstinence on blood pressure: assessment by 24-hour ambulatory blood pressure monitoring.

Several studies have shown that cessation of alcohol drinking reduces blood pressure (BP). However, attempts to reproduce these findings by ambulatory BP monitoring (ABPM) have shown inconsistent results. The aim of the present study was to assess the effect of 1 month of proven abstinence from alcohol on the 24-hour BP profile in heavy alcohol drinkers. Forty-two men who were heavy drinkers (>100 g of pure ethanol per day) were consecutively admitted to a general ward for voluntary alcohol detoxification. On the day of admission, they received a total dose of 2 g/kg of ethanol diluted in orange juice in 5 divided doses, and a 24-hour ABPM was performed. A new 24-hour BP monitoring in the same environmental conditions was performed after 1 month of proven alcohol abstinence while the subjects were receiving the same amount of fluid but without the addition of alcohol. After 1 month of proven alcohol abstinence, BP and heart rate (HR) significantly decreased. The reduction was 7.2 mm Hg for 24-hour systolic BP (SBP) (95% CI, 4.5 to 9.9), 6.6 mm Hg for 24-hour diastolic BP (DBP) (95% CI, 4.2 to 9.0), and 7.9 bpm for HR (95% CI, 5.1 to 10.7). The proportion of alcoholic patients considered hypertensive on the basis of 24-hour BP criteria (daytime SBP >/=135 mm Hg or daytime DBP >/=85 mm Hg) fell from 42% during alcohol drinking to 12% after 1 month of complete abstinence. Abstinence did not modify either the long-term BP variability, assessed by SD of 24-hour BP, or its circadian profile. We conclude that abstinence in heavy alcohol drinkers significantly reduces BP assessed by 24-hour ABPM and that this reduction is clinically relevant. These results show that heavy alcohol consumption has an important effect on BP, and thus cessation of alcohol consumption must be recommended as a priority for hypertensive alcohol drinkers.

Erythrocyte sodium transport, intraplatelet pH, and calcium concentration in salt-sensitive hypertension.

We evaluated changes in erythrocyte sodium transport systems, platelet pH, and calcium concentration induced by low and high salt intakes in a group of 50 essential hypertensive patients classified on the basis of their salt sensitivity. Patients received a standard diet with 20 mmol NaCl daily for 2 weeks supplemented in a single-blind fashion by placebo tablets the first 7 days and NaCl tablets the following 7 days. Salt sensitivity, defined as a significant rise (P <.05) in 24-hour mean blood pressure obtained by ambulatory blood pressure monitoring, was diagnosed in 22 (44%) patients. The remaining 28 (56%) were considered to have salt-resistant hypertension. In the entire group of hypertensive patients, high salt intake promoted a significant increase (P <.05) in the maximal rate of erythrocyte NA(+)-Li(+) countertransport (from 271 +/- 19 to 327 +/- 18 microM/(L cells/h) and of the Na(+)-dependent HCO3(-)-CL(-) exchanger (from 946 +/- 58 to 1237 +/- 92 microM/L cells/h) as well as in platelet pH (from 7.15+/-0 0.01 to 7.19+/-0.02 and calcium concentration (from 49+/-2 to 57 +/-2 nmol/L). Depending on salt sensitivity, high salt intake promoted opposing changes in some of the sodium transport systems studied. Salt-sensitive patients increased the maximal rate of the erythrocyte Na(+)-K(+) pump (fom 7.0 +/- 0.4 to 8.8 +/- 0.4 mmol/(L cells/h), Na(+)-K(+)-Cl(-) cotransport (from 416 +/- 37 to 612 +/- 41 micromol/(L cells/h), Na(+)-Li(+) countertransport (from 248 +/- 20 to 389 +/- 17 micromol/(L cells/h) at the end of the high salt period. Conversely, salt-resistant patients decreased the Na(+)-K(+) pump (from 8.0 +/- 0.4 to 6.9 +/- 0.3 mmol/(L cells/h) and Na(+)-K(+)-Cl(-) cotransport (from 578 +/- 53 to 481 +/- 43 micromol/(L cells/h). We conclude that modulation of erythrocyte sodium transport systems by high salt intake depends on salt sensitivity. The Na(+)-K(+) pump, Na(+)-K(+)-Cl(-) cotransport, and Na(+)-Li(+) countertransport increase in salt-sensitive patients, whereas the activity of these sodium transport systems tends to decrease in salt-resistant patients. Independent of salt sensitivity, high salt intake promotes a significant increase in the erythrocyte Na(+)-dependent HCO3(-)-Cl(-) exchanger, platelet pH, and calcium concentration in essential hypertensive patients.

Na+-Li+ countertransport in essential hypertension.

Several studies on Na+-Li+ countertransport have reported higher rates in essential hypertensive than in normotensives, with a distribution pattern which is dependent on racial and ethnic background. However, it is not well established whether this abnormality in Na+ transport is associated with an abnormal clinical setting. In the present study we have performed a kinetic analysis of the interaction of the Na+-Li+ countertransport system with internal Na+ in erythrocytes from a sample of 72 essential hypertensives and 30 normotensive controls. A significant increase in mean values of the maximal rate of Li+-stimulated Na+ efflux (Vmax; 375.1 +/- 23.8 versus 213.7 +/- 8.5 mumol/l cells per h; mean +/- s.e.m.; Mann-Whitney test: U = 500; P less than 0.0001), as well as in the apparent affinity constant for internal Na+ (KNa; 10.03 +/- 0.08 versus 6 +/- 0.4 mmol/l cells; Mann-Whitney test: U = 718; P less than 0.0079), were observed in essential hypertensives with respect to normotensives. Using the 95% confidence interval of Vmax in normotensives as the normal range, 29 (40.3%) of the essential hypertensives exhibited values above the normal upper limit. The maximal rate (Vmax) and the internal Na+ content required for half-maximal stimulation (K50%) of Na+-K+ ATPase and outward Na+-K+ cotransport, and the rate constant of Na+ leak (KPNa) in this subset were similar to the values observed in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetic study of the Ca2+ pump in erythrocytes from essential hypertensive patients.

Ca2+ pump kinetics were investigated in erythrocytes from 22 essential hypertensive patients and 20 normotensive controls (under initial-rate and steady-state conditions, using Sr2+ as a Ca2+ analogue). The mean value of the apparent dissociation constant for total internal Ca2+ (KCa) was slightly but significantly increased in the hypertensive population (73 +/- 7 versus 55 +/- 3 mumol/l cells, mean +/- s.e.m., P = 0.042 Mann-Whitney U-test). The statistical analysis showed that this was due to six essential hypertensives who exhibited a dissociation constant for Ca2+ that was higher than the upper 95% normal confidence limit (KCa = 116 +/- 7 mumol/l cells), and abnormally high maximal pump rates (7.7 +/- 0.6 versus 5.0 +/- 0.2 mmol/l cells per h in normotensives, P less than 0.001). In addition, the apparent dissociation constant for Ca2+ was inversely correlated with plasma renin activity, although the correlation was only borderline (P = 0.076). In the remaining 16 hypertensive patients, all kinetic parameters of the Ca2+ pump were within the normal range. Finally, a simultaneous study of Na+ transport kinetics suggested that erythrocyte Ca2+ and Na+ transport abnormalities were independent phenomena. Our results do not support the concept that primary hypertension (as a whole entity) is associated with a ubiquitous defect in the plasma membrane Ca2+ pump. However, in some essential hypertensive patients (about 25%) the erythrocyte Ca2+ pump exhibited an apparent decreased affinity for internal Ca2+. A similar defect in vascular smooth muscle may induce a delayed Ca2+ extrusion after the opening of Ca2+ channels, a disturbance likely to be translated into increased vascular reactivity.