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In 1985, investigators characterized a potent vasoconstrictor of endothelial origin called endothelin (ET). Subsequently, 3 peptides were recognized that had a comparable molecular structure but different receptors that mediate potent vasoconstrictive and mild vasodilative effects. The renal effects are characterized by natriuresis despite renal vasoconstriction. This effect, along with the stimulation of ET by high sodium intake, suggests that ET may be responsible for maintaining sodium balance when the renin-angiotensin system is depressed. Endothelin is activated in desoxycorticosterone acetate salt hypertension models and salt-sensitive hypertension. However, ET involvement with spontaneous hypertension models and renovascular hypertension in rats appears minimal. In humans, the role of ET appears similar to that in experimental animals; in both, ET regulates salt metabolism. Salt-sensitive patients exhibit a blunted renal ET-1 response during sodium load. The role of ET in humans has been investigated using nonspecific ET receptor blockers that inhibit the vasoconstrictive and vasodilative components of ET. However, the effects of ET blockade should be investigated with ET subtype A receptor blockers that mediate vasoconstriction alone. Effects of ET blockade also should be evaluated with respect to stimulation of oxidative stress and tissue damage, important mechanisms responsible for tissue fibrosis. This review offers the clinician a balanced view on the hypertensive mechanisms involved with activation of ET and associated clinical implications. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is a rather common chronic disorder, associated with increased prevalence of hypertension. The pathophysiological mechanisms for hypertension in OSA are at least in part linked to intermittent hypoxia developed during nightly hypopneas and apneas. Hypoxemia stimulates sympathetic overactivity, systemic inflammation, oxidative stress, and endothelial dysfunction. However, it appears that intermittent hypoxemia is not the only factor in the development of hypertension in OSA. Supplemental oxygen therapy that improved oxyhemoglobin saturation to similar levels to those achieved with CPAP treatment did not reduce BP. In this scenario, it could be proposed that hypoxemia acts as a trigger of sympathetic overdrive, which when set is the main factor in the development of hypertension in OSA. This review appraises evidence provided by randomized controlled trials on the BP-lowering effectiveness of continuous positive airway pressure (CPAP) treatment of OSA patients with nonresistant and resistant hypertension. It suggests that CPAP treatment is more effective in treating resistant hypertension than nonresistant hypertension. A possible explanation is that sympathetic overactivity and altered vascular reactivity in OSA could be more severe in resistant hypertension than in nonresistant hypertension. An intricate interaction among compliance, adherence, and their interaction with demographic characteristics, genetic factors, and comorbidities of the population included might explain the differences found between trials on their influence over the antihypertensive effectiveness of CPAP. Further long-term trials are needed in hypertensive OSA patients to assess whether CPAP treatment in OSA patients consistently restores physiological nocturnal BP fall and adjusts resting and circadian heart rate.

Albeit hypertension is a leading risk factor for an initial stroke, the role of blood pressure (BP) lowering to prevent a subsequent stroke is controversial. The present systematic review searched randomized trials published from January 1990 to January 2014 with the aim to assess antihypertensive treatment effects on recurrent stroke prevention. Seven randomized placebo-controlled trials enrolling 49,518 patients, two randomized trials not placebo controlled comparing antihypertensive drugs, and one randomized trial that compared the effects of intensive systolic BP lowering with a more conservative systolic BP management, were identified. The placebo-controlled trials had substantial methodological differences, explaining the difficulties to compare their results. An important obstacle arises from the large dispersion in the window's time between the qualifying stroke and randomization. Another barrier is the variation among studies in the recruited patient's stroke subtypes. Differences between trials could not be attributed to disparity in lowering BP or to different degrees of no adherence. The American Heart Association/American Stroke Association stated that although an absolute target of BP level has not been clearly defined, a reduction in recurrent stroke has been associated with an average lowering of 10/5 mm Hg. It should be taken into account that it is not advisable to reduce BP levels to <120/80 mm Hg. It should carry out an individualized selection, based on demographic characteristics and comorbidities (cardiovascular disease, diabetes mellitus, and chronic disease) among diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, or calcium channel blockers., (Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Hypertension is the leading risk factor for ischemic and intracerebral hemorrhagic subtypes of stroke. Additionally, high blood pressure (BP) in the acute cerebrovascular event is associated with poor outcome, and a high percentage of stroke survivors have inadequate control of hypertension. The present is a systematic review of prospective, randomized, and controlled trials carried out on safety and efficacy of antihypertensive treatment of both subtypes of acute stroke. Six trials involving 7512 patients were included, which revealed controversies on the speed and the goals of treatment. These controversies could be due at least in part, from the fact that some studies analyzed the results of antihypertensive treatment in ischemic and intracerebral hemorrhagic subtypes of acute stroke together, and from a different prevalence of past-stroke in the randomized groups. Further research is necessary to establish whether standard antihypertensive treatment provides greater benefit than simple observation in patients with ischemic acute stroke and Stage 2 hypertension of JNC 7, albeit they were not candidates for acute reperfusion. In that case, the target reduction in BP could be 10% to 15% within 24 hours. The recently published INTERACT 2 has provided evidence that patients with hemorrhagic stroke may receive intensive antihypertensive treatment safely with the goal of reducing systolic BP to levels no lower than 130 mm Hg. It is important to take into account that marked BP lowering in acute stroke increases the risk of poor outcome by worsening cerebral ischemia from deterioration of cerebral blood flow autoregulation., (Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Nocturia is a risk factor for morbidity and mortality but is frequently overlooked and underreported by patients and unrecognized by physicians. Epidemiologic studies reported that nocturnal voiding is associated not only with aging and benign prostatic hyperplasia, but also with many other clinical conditions. The majority of epidemiologic studies reported a significant relationship between nocturia and hypertension. However, the cause-and-effect relationship between them has not been established. Some physiopathological changes in hypertension are conducive to result in nocturia. These include the effects of hypertension on glomerular filtration and tubular transport, resetting of the kidney pressure-natriuresis relationship, atrial stretch and release of atrial natriuretic peptide when congestive heart failure complicates hypertension, and peripheral edema. Another link between hypertension and nocturia is obstructive sleep apnea. Furthermore, some evidence supports the relationship between nondipping behavior of blood pressure and an increased prevalence of nocturia. The use of some classes of antihypertensive agents may result in nocturia. The present review aims to provide a comprehensive evaluation of the epidemiologic evidence and physiopathological links that correlate hypertension and nocturia. Emphasis is placed on the need to take a pro-active attitude to detect and treat this hazardous condition., (Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Epidemiological studies suggest an association between chronic blood pressure (BP) changes and Alzheimer's disease (AD). In particular, there is growing evidence that hypertensive people that do not have their BP adequately treated and controlled in midlife are more likely to develop AD in late-life. It has been hypothesized that cerebrovascular disease is a common pathway which connects hypertension and AD in individuals with apolipoprotein E genotype through brain hypoperfusion and hypoxia. This could accelerate amyloid-β aggregation that disrupts cell-to-cell connectivity and leads to eventual brain neuron loss. Also, high BP contributes to worsen AD by raising oxidative stress and inflammatory response. Aging-related structural and functional disturbances appear to exacerbate the deleterious effect of chronic hypertension on cerebral blood flow autoregulation. There is evidence suggesting that some antihypertensive drug classes reduce the risk and progression of AD more than others. Further prospective randomized studies comparing different classes of antihypertensive drugs are needed to provide more evidence regarding their effects on AD risk. Hypotension could be a consequence of the incident dementia and conversely deteriorate the outcome of AD by worsening brain hypoperfusion. Frequent home BP monitoring should be carried out in AD patients to detect harmful orthostatic hypotension.

Our aims were to evaluate the prevalence and outcome of hypertension in patients with primary hyperparathyroidism (PHPT), previously and after follow-up of parathyroidectomy. A group of 46 consecutive patients with sporadic PHPT due to adenoma undergoing surgery were followed an average of 3.5 years (range 36 to 53 months). In 16 nonselected, consecutive parathyroidectomized patients, with normalized biochemical measurements, circadian rhythm of blood pressure was evaluated with ambulatory blood pressure monitoring (ABPM). Prevalence of hypertension in PHPT was 54.35%, and there was no significant association of PTH, total and ionic calcium levels with SBP and DBP. During follow-up, none of the patients with presurgical hypertension became normotensive and five of the normotensive patients developed clinical hypertension. In ABPM, 6/11 hypertensive and 3/5 normotensive subjects showed nondipper behavior. Serum total calcium was significantly related to night-time systolic blood pressure (SBP) (r = 0.620, P < 0.02), and night-time diastolic blood pressure (DBP) (r = 0.758, P < 0.002). In dippers, creatinine clearance was significantly higher (91.3 +/- 18.5 vs. 64.3 +/- 11.5 ml/min, P < 0.01), while serum total calcium was lower (2.42 +/- 0.13 vs. 2.23 +/- 0.17 mmol/L, P < 0.04) than in nondippers. In conclusion, our results suggest that parathyroidectomy has little effect on hypertension prevalence. Renal impairment, a condition that did not improve after parathyroidectomy, may be a causal factor of hypertension in PHPT. Also, the high prevalence of nondipper behavior in hypertensive and normotensive subjects after parathyroidectomy, suggests that target organ risk persists. We hypothesized that slight elevations of serum total calcium even in the normal range could be involved in the alteration of the circadian rhythm of blood pressure.

High blood pressure is a very common disease in hypercholesterolemic and diabetic patients and contributes to the increase in cardiovascular risk. Inhibitors of 3OH-3methyl-glutaryl-coenzyme A reductase are the most effective and widely used cholesterol-lowering drugs. They significantly reduce the risk of cardiovascular events and death in both primary and secondary prevention of cardiovascular disease. Although the long-term benefit by statin treatment is largely attributed to their cholesterol-lowering action, increasing attention focuses on additional actions called "pleitropic effects" that might explain the cardiovascular protection seen shortly after the initiation of therapy. Very few and small studies have investigated the antihypertensive effect of statins in patients with hypertension associated with hypercholesterolemia, and the results of recently published large statin studies (albeit not designed to answer this question) have attracted the interest on this subject. Many other studies, also not specifically aimed at the evaluation of the statins' antihypertensive effect, have provided information concerning changes in blood pressure during treatment with statins, but severe limitations such as inadequate study design, small or very small sample size, too short of a treatment period, and modification of concomitant antihypertensive therapy have prevented finding a definitive effect on blood pressure. From the available results, it appears consistent that statins may be useful in hypertensives with high serum total cholesterol, in those whose hypertension is not well controlled with antihypertensive agents even without high serum total cholesterol, in hypertensive subjects well controlled with antihypertensives without high serum cholesterol when they have high polymerase chain reaction levels, in those who require preventive measures because of other concomitant cardiovascular risk factors, or when they require secondary prevention. Future research could further characterize the impact of statin use alone or in combination with antihypertensive agents to delay the development of Stage 1 hypertension in prehypertension.

Alzheimer's disease is the most frequent cause of dementia. Whereas other major causes of death have been decreasing, the number of deaths due to Alzheimer's disease is rising. As there is no cure for this type of dementia at present, preventive measures have assumed great importance. By analyzing data from available longitudinal studies, the current review presents evidence supporting a link between Alzheimer's disease and blood pressure changes., (Copyright © 2010 S. Karger AG, Basel.)

The beneficial effects of statins in hypertension stem from their effects on endothelial function, their interactions with the renin-angiotensin system, and their influence on large artery compliance. Substantial evidence has recently accumulated showing that statins exert pleiotropic effects in vascular function. These include an increase in the synthesis of NO, inhibition of vascular smooth muscle cell proliferation and migration, anti-inflammatory actions, downregulation of angiotensin II type 1 receptor expression, and anti-oxidative effects. These effects occur before reduction of cholesterolemia. Available data support only a modest BP-lowering effect of statins which is most prominent in those patients with poorly controlled hypertension. Even though they only cause a minor reduction in BP, they may play a role in the prevention of cardiovascular disease. Statins may be useful therapeutic agents in hypertensives with high serum total cholesterol, in patients with poorly controlled hypertension even without hypercholesterolemia, in normocholesterolemic well-controlled hypertensive subjects with high C reactive protein levels, and in those subjects who need secondary prevention. Future research is needed to further characterize the impact of statins alone or in combination with antihypertensive agents to prevent or delay the development of stage 1 hypertension. This review article also includes relevant patents.

Resistant hypertension, defined as a persistent blood pressure over 140/90 mmHg despite the use of three antihypertensive drugs including a diuretic, is unusual. The diagnosis requires ruling out initially pseudoresistance and a lack of compliance with treatment. Ambulatory blood pressure recording allow the recognition of white coat hypertension. When there is a clinical or laboratory suspicion, secondary causes of hypertension should be discarded. Excessive salt intake, the presence of concomitant diseases such as diabetes mellitus, chronic renal disease, obesity, and psychiatric conditions such as panic attacks, anxiety and depression, should also be sought. The presence of target organ damage requires a more aggressive treatment of hypertension. Recent clinical studies indicate that the administration of aldosterone antagonists as a fourth therapeutic line provides significant additional blood pressure reduction, when added to previous antihypertensive regimens in subjects with resistant hypertension. The possible blood pressure lowering effects of prolonged electrical activation of carotid baroreceptors is under investigation.

Background and Aim: To examine the relationship between 24-h ambulatory blood pressure monitoring (ABPM) and three commonest anthropometric measurements for obesity [body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR)] in patients with essential hypertension never treated or after a 3 week placebo period, living in Buenos Aires., Methods and Results: Cross-sectional survey among outpatients at the Hypertension Program of Buenos Aires University Hospital de Clinicas. Three-hundred seventy-seven essential hypertensives, aged 18-86 years, of either sex, were consecutively recruited. All subjects underwent 24 h ABPM performed with a blood pressure (BP) device. The prevalence of overweight-obesity was 56.76% in women and 75.86% in men. High WHR prevalence in non-obese women was 4.5% and 4.1% in non-obese men while high values of WC were observed in 3.0% of non-obese women and in 0% of non-obese men. The two-way ANCOVA showed that in women with high values of WHR, 24 h DBP was higher in those with BMI<25 than in those with BMI> or =25. Those females with a BMI> or =25 had a higher prevalence of top tertile values of PP (> or =68 mmHg) (P<0.05) than non-obese females. Only in women was mean pulse pressure (PP) significantly correlated with age (r=0.38; P<0.0001), WC (r=0.22; P<0.005), WHR (r=0.21, P<0.008), and BMI (r=0.20; P<0.01) while in men there was no significant correlation between variables. Logistic regression showed that the odds of morning blood pressure surge (MBPS) increased with age, central obesity (represented by high WHR and dipper status), while the odds of higher mean PP increased with age and high WHR., Conclusion: These results indicated a high prevalence of overweight-obesity (more than 56% of women and 75% of men) in our hospital-based sample of essential hypertension and that the WHR offers additional information beyond BMI and WC to predict the hypertension risk according to the ABPM.

Background: Type 2 diabetes and essential hypertension are the most common causes of end-stage renal disease in Argentina. Over 887 organ transplantations performed in the year 2004, 577 were kidney transplants. In urban and rural populations hypertension was more prevalent in type 2 diabetics, in particular systolic hypertension. Outcome studies are used to measure clinically meaningful primary end points, such as mortality and cardiovascular morbidity. Our current knowledge of the effects of antihypertensive agents on cardiovascular risk in hypertensive patients with type 2 diabetes has been achieved from subgroups included in large-scale studies., Scope: The present study, based on a search of MEDLINE literature in the period 1990-2005, revised major randomised studies with the purpose of finding out which are the most advisable therapeutic strategies against this morbid association. The majority of patients require 2 to 4 antihypertensive medications to achive BP levels that correlate with diminished progression of target organ damages. Despite the advantages of renin-angiotensin system inhibitors the initial choice of medications should be based on the evidences of target organ damages. In those patients without any evidence of complications, the primary goal seems to be achieving their BP to < 130/80 mm Hg beyond the differences among antihypertensive drugs classes, while in those with target organ damage evidences maintain BP < 120/75 mm Hg.

In 1985, investigators characterized a potent vasoconstrictor of endothelial origin called endothelin (ET). Subsequently, 3 peptides were recognized that had a comparable molecular structure but different receptors that mediate potent vasoconstrictive and mild vasodilative effects. The renal effects are characterized by natriuresis despite renal vasoconstriction. This effect, along with the stimulation of ET by high sodium intake, suggests that ET may be responsible for maintaining sodium balance when the renin-angiotensin system is depressed. Endothelin is activated in desoxycorticosterone acetate salt hypertension models and salt-sensitive hypertension. However, ET involvement with spontaneous hypertension models and renovascular hypertension in rats appears minimal. In humans, the role of ET appears similar to that in experimental animals; in both, ET regulates salt metabolism. Salt-sensitive patients exhibit a blunted renal ET-1 response during sodium load. The role of ET in humans has been investigated using nonspecific ET receptor blockers that inhibit the vasoconstrictive and vasodilative components of ET. However, the effects of ET blockade should be investigated with ET subtype A receptor blockers that mediate vasoconstriction alone. Effects of ET blockade also should be evaluated with respect to stimulation of oxidative stress and tissue damage, important mechanisms responsible for tissue fibrosis. This review offers the clinician a balanced view on the hypertensive mechanisms involved with activation of ET and associated clinical implications.

Diabetes mellitus affects approximately 135 million people in the world. Diabetes and hypertension are both relatively common diseases in westernised countries. Both entities increase with age. Essential hypertension accounts for the majority of hypertension in people with type 2 diabetes, who constitute more than 90% of those with a dual diagnosis of diabetes and hypertension. The benefit conferred per mm Hg blood pressure reduction appears to be greater in persons with type 2 diabetes than in those with hypertension and non-coexistent diabetes mellitus. Similar to a subset of patients with essential hypertension, type 2 diabetic patients manifest dietary NaCl-induced exacerbation of hypertension. Recent guidelines have emphasised that the target blood pressure levels for patients with diabetes should be lower than in other hypertensive groups. An increased total body sodium and enhanced vascular reactivity are found in people with diabetes and most type 2 diabetic patients are salt sensitive. Type 2 diabetes with hypertension is associated with reduced renal plasma flow when dietary salt intake is high. Experimental, observational and interventional evidence support the benefits of sodium restriction in hypertensives. However, the full effects of sodium restriction are usually not obvious for at least 5 weeks. Other favourable effects of moderate reduction in sodium intake are a regress left ventricular hypertrophy, decrease in diuretic-induced potassium wastage, reduction in proteinuria, protection against stroke and from osteoporosis and renal stones, and enhancement of the antihypertensive effect of the antihypertensive agents.

The aim of the study was to elucidate the role of hyperinsulinaemia/insulin resistance in hypertension of lean postmenopausal women. Twenty-four women with essential hypertension (systolic/diastolic > or =140/90 mm Hg) and a body mass index (BMI) less than 26 kg/m(2) not receiving antihypertensive treatment or who had been without treatment for a 4-week washout period, and 10 normotensive postmenopausal weight- and aged-matched controls were compared. Both groups were not receiving hormone replacement therapy. Hip and waist circumferences were measured and waist/hip ratios were calculated. Casual blood pressure was measured in triplicate. Neither the fasting plasma glucose nor serum insulin levels in hypertensive women and normotensives differed significantly. During 2 h oral glucose (75 g)-tolerance test the mean plasma glucose levels after 30 min (172.5 +/- 40.24 mg/dl vs. 143.67 +/- 20.16 mg/dl), 60 min (134.88 +/- 38.78 mg/dl vs. 112.33 +/- 5.44 mg/dl) and 120 min (116.08 +/- 26.65 mg/dl vs. 95.56 +/- 20.17 mg/dl) were significantly higher in hypertensives than that for normotensives (P < 0.05 for all three comparisons). The mean serum insulin levels of hypertensive women were significantly higher than that in normotensives after 15 min (92.04 +/- 59.90 microU/ml vs. 54.89 +/- 33.67 microU/ml) and 120 min (49.63 +/- 44.45 microU/ml vs. 19.22 +/- 24.10 microU/ml; P< 0.05 for both comparisons). The mean serum insulin: plasma glucose ratio for hypertensive women was significantly higher than that for normotensives after 15 min (0.596 +/- 0.46 vs. 0.359 +/- 0.20 microU/mg), 60 min (0.406 +/- 0.30 vs. 0.329 +/- 0.25 microU/mg) and 120 min (0.436 +/- 0.35 vs. 0.205 +/- 0.26 microU/mg) (P < 0.05 for all three comparisons). Significant correlations were observed between the daytime period and 24-h average ambulatory systolic blood pressure and the area under the serum insulin curve (r = 0.41 and 0.36, respectively). For non-dippers we found higher fasting insulinaemias but the AUC(insulin) did not differ. Plasma glucose levels did not differ either during fasting or during OGTT (AUC(glucose)). Insulinogenic index was higher in dippers than in non-dippers. We conclude that in lean, postmenopausal hypertensive women insulin resistance is increased compared with age- and weight-matched normotensive women. Also, hyperinsulinaemia correlates with ambulatory systolic blood pressure. Thus, insulin resistance may possibly be involved as a pathogenetic factor in lean, postmenopausal hypertensive women.

Sibrafiban (G-7453) is an orally active non-peptide GPIIb/IIIa antagonist, under development by Genentech and Hoffmann-La Roche, and in phase III trials as an antithrombotic. Roche intends to file for marketing approval in 1999. Merrill Lynch predicts a product launch in 2001.

Objective: To elucidate the role of hypertension as part of a state of insulin resistance., Methods: Thirty-one uncomplicated hypertensive men not receiving antihypertensive treatment or who had been without treatment for a 4-week washout period and 10 lean normotensive controls were compared. Hypertensive men were divided according to their body mass index into three groups. All subjects came to the clinic for measurements of height, weight, hip and waist circumferences, and sitting blood pressure, and to begin 24 h ambulatory blood pressure monitoring. Plasma glucose and insulin levels were measured during a 2 h oral glucose (75 g)-tolerance test. For the hypertensive population as a whole, behaviors of studied variables among dippers (n = 18) and nondippers (n = 13) were determined., Results: During oral glucose-tolerance testing blood glucose levels after 60 min and 120 min were significantly higher (P < 0.05) in members of the high body mass index group than they were in members of the low body mass index group. Insulin levels of members of the high and middle body mass index groups were higher than those of members of the low body mass index group after 60 min (P < 0.05 for both comparisons) and 120 min (P < 0.05 for both comparisons). The mean serum insulin level in members of the low body mass index group was significantly higher than that in normotensives after 30 min, 60 min and 120 min (P < 0.05 for all three comparisons). The mean serum insulin: plasma glucose ratio for men in the low BMI group was significantly higher than that for normotensives after 60 min and 120 min (P < 0.05 for both comparisons). Correlations of blood pressure and insulin levels were not significant. Levels of high-density lipoprotein cholesterol and triglycerides were lower in members of the group with high body mass index than they were in members of the group with low body mass index. Total cholesterol: high-density lipoprotein cholesterol ratio was higher for members of the high body mass index group than it was for members of the middle body mass index group. Weight, body mass index, casual systolic blood pressure, 24 h average systolic blood pressure and diastolic blood pressure, 0700-2300 h systolic blood pressure, and 24 h average heart rate-systolic blood pressure product of dippers were significantly lower than those of nondippers., Conclusions: These results suggest that hypertension and being overweight have additive effects increasing insulinemia and that being overweight is associated with a significantly lower nocturnal fall in blood pressure.

Diabetic patients suffer from atherosclerosis and its complications more frequently and at an earlier stage than nondiabetic people. The factors predisposing diabetics to premature arteriosclerosis are not fully clarified. Data from a 5-year follow-up of 617 diabetics, 376 non-insulin dependent (NIDDM) and 241 insulin-dependent (IDDM), attending the Hospital de Clínicas José de San Martín at Buenos Aires city are reported. By the WHO criteria 55% of NIDDM and 29% of IDDM had hypertension. Hypertension was significantly (p less than 0.01) more common among NIDDM than among IDDM patients after adjustment for age, sex and obesity. The incidence of angor pectoris, acute myocardial infarction and heart failure was significantly greater in hypertensive patients of both types of diabetes than in the respective normotensive group. No sex differences were observed in both diabetic groups in the incidence rates of coronary heart disease. Overt diabetic nephropathy and diabetic retinopathy were more frequent in hypertensives than in normotensives of both groups of diabetics. Even though 63% of hypertensive patients with NIDDM and 57% with IDDM received antihypertensive treatment only 36% and 24% respectively had their blood pressure well controlled. Acute myocardial infarction was the most frequent cause of death in both NIDDM and IDDM hypertensive people.

In a randomized double-blind study (N = 562), a traditional treatment schedule, starting antihypertensive treatment in elderly hypertensive patients (60 to 75 years old) with 25 mg of hydrochlorothiazide once daily and doubling the dose if a satisfactory response was not achieved, was compared with antihypertensive treatment of 100 mg of metoprolol once daily, adding 12.5 mg of hydrochlorothiazide for patients whose response was not satisfactorialy achieved with metoprolol alone. Systolic and diastolic blood pressure was significantly reduced with both regimens. The frequency rates of responders (diastolic blood pressure, less than or equal to 95 mm Hg) in the metoprolol group and the hydrochlorothiazide group were 50% and 47% after four weeks and 65% and 61% after eight weeks, respectively. There were no significant differences in total symptom score or single symptoms between the regimens, but significantly more patients had hypokalemia and hyperuricemia with the hydrochlorothiazide regimen. Thus, we conclude that beginning antihypertensive treatment with 100 mg of metoprolol once daily and adding a small dose of hydrochlorothiazide (12.5 mg) in patients whose response is not satisfactory with metoprolol alone appears to be effective and safe in elderly hypertensive patients.

Pulmonary and systemic hemodynamics in 28 mild to moderate hypertensive patients (group II) with left ventricular (LV) hypertrophy (ECG and echo criteria) and 22 severe hypertensive patients with LV hypertrophy (group III) were compared with 20 patients with mild-to-moderate hypertension in WHO stage I (group I). Mean right atrial pressure was equivalent in groups II and III and significantly higher in the last group than in group I. An increased pulmonary arterial resistance (PAR) in group II and, to a large extent, in group III accounted for the elevation of diastolic and mean pulmonary arterial pressure in both groups in comparison with group I. Cardiac index (CI) was lower and systemic vascular resistance (SVR) higher in group III than in group I. Pulmonary capillary wedge pressure (PCWP) values were within the normal range and equivalent between groups II and III, and both significantly higher than in group I. PAR showed a positive relation with SVR (r = 0.30, P less than 0.01) and an inverse relation with CI (r = -0.561, P less than 0.001). Findings indicate that in systemic hypertension with LV hypertrophy there is an elevation of the right ventricular filling pressure and the pulmonary arterial pressure whose degree is even higher in severe hypertension. This increase is not necessarily a consequence of impairment of LV function as suggested by the normal range of PCWP values.

In a randomised double-blind study the effects on left ventricular mass (LV mass) and cardiac haemodynamics of urapidil, an antihypertensive agent with a vascular postsynaptic alpha 1-blocking action and a central antihypertensive effect, were compared with those of methyldopa in 29 patients with essential hypertension. During a 3-month period, urapidil was initially given at 120 mg/day and increased to 180 mg/day if a satisfactory antihypertensive response was not achieved. Methyldopa was started at 100 mg/day and increased to 1500 mg/day if an adequate blood pressure response was not achieved. Echocardiographic measurements were obtained at baseline and after 12 weeks' active treatment. The frequency rates of responders (DBP less than 95 mm Hg) on urapidil and methyldopa were 54% and 62%, respectively, after 12 weeks. In the group as a whole there was a nonsignificant tendency for decreased LV mass on both active drugs. However, the haemodynamic changes were difficult to interpret because of baseline differences between the 2 treatment groups.

Hemodynamic evaluation of three men and eight women aged 20 to 58 years (mean, 44 years) with essential hypertension was performed before and after a single dose of guanfacine and before and after long-term administration of the drug, which is a stimulant of central alpha-adrenergic receptors. Mean (+/- SE) recordings of blood pressure before catheterization were 168/115 +/- 6/3 mmHg when supine and 168/112 +/- 8/4 mmHg when standing. Within two hours of oral administration of 3 mg of guanfacine, the heart rate decreased from a mean of 77 +/- 2 to 69 +/- 3 beats/min (P less than 0.05), and the pulmonary capillary wedge pressure (PCWP) decreased from a mean of 9 +/- 1 to 6 +/- 1 mmHg (P less than 0.02). The mean readings of pulmonary arterial pressure also decreased, as follows: systolic, from 22 +/- 2 to 18 +/- 0.14 mmHg (P less than 0.05); diastolic, from 9 +/- 1 to 7 +/- 1 mmHg (P less than 0.05); and mean, from 15 +/- 1 to 12 +/- 2 mmHg (P less than 0.05). No changes were observed in systemic blood pressure, the cardiac index, systemic vascular resistance, or total pulmonary vascular resistance. After a six-week course (mean dosage, 3.9 +/- 0.57 mg/day), the following variables decreased significantly: systemic blood pressure--systolic, diastolic, and mean, both supine and standing (P less than 0.001); heart rate (P less than 0.001); and systemic vascular resistance (P less than 0.01). The PCWP reached values similar to those measured during the control phase. Increases were noted in pulmonary artery systolic pressure (P less than 0.05), mean right atrial pressure (P less than 0.01), and in the stroke volume index (P less than 0.05). It is likely that the main hemodynamic mechanism underlying the long-term antihypertensive effect of guanfacine is a decrease in systemic vascular resistance.

This study compares the sympathetic nervous system response to graded exercise in normotensive and essential hypertensive subjects with and without beta-adrenergic blockade. Blood pressure (BP), heart rate, and plasma norepinephrine (NE), epinephrine (E), and dopamine (DA) were measured just before starting the exercise (Pre-Ex), in the submaximal exercise (Sub-max),and after 8 minutes rest (Post-Ex). On placebo, Sub-max induced in both normotensives and hypertensives a similar increase in NE and E plasma levels. Plasma DA remained unchanged. Propranolol in controls and propranolol or mepindolol in hypertensives didn't modify significantly: 1) Pre-Ex plasma levels of E, NE, and DA; 2) response at Sub-max in controls; 3) plasma E and DA in hypertensive patients. In hypertensives on beta-blockade, submaximal exercise elicited a greater increase in plasma NE. Values for plasma NE in patients on propranolol were 1135 +/- 229 pg/ml higher than those obtained in the same patients on placebo (p less than 0.001). On mepindolol, the plasma NE increment was higher than that on placebo (p less than 0.05), but lower than that on propranolol (p less than 0.01). In controls, propranolol did not significantly modify BP at Pre-Ex or its response to exercise, whereas systolic and diastolic BP were significantly lower at Pre-Ex, Sub-max, and Post-Ex in hypertensives. On beta-blockade, heart rate decrease in Pre-Ex, Sub-max, and Post-Ex were not different in controls and hypertensives. The differences found on beta blockade would indicate that the effects of beta blockers are not identical in normotensive and hypertensive subjects.