Association of carotid intima-media thickness and cardiovascular risk factors in women pre- and post-bariatric surgery.

BACKGROUND: Obesity is associated with cardiovascular risk factors (CVRFs), such as hypertension, hypertriglyceridemia, and low levels of high-density cholesterol (HDL-C). In obese patients with a body mass index (BMI) of >or=40 kg/m2 or 35-40 kg/m2 associated with CVRFs, weight loss may be achieved more effectively by bariatric surgery on reducing several CVRFs. Carotid intima-media thickness (C-IMT) is an indicator of early atherosclerosis, and may be correlated with CVRFs. Our objective was to correlate C-IMT with CVRFs before (baseline data) and after surgery, and to observe whether weight loss is followed by a regression of C-IMT. METHODS: Eighteen women who had undergone bariatric surgery participated in this study. Assessments were carried out on the baseline date, and 3, 6, and 12 months after surgery. Some of the CVRFs analyzed were: total cholesterol (TC) levels, HDL-C, triglycerides to HDL-C ratio (TG/HDL-C) and fasting plasma glucose. C-IMT was measured by B-mode ultrasound. RESULTS: A positive correlation was found between C-IMT and age and triglyceride level (p=0.002 and p=0.02, respectively). Six months after surgery, we found a significant reduction in C-IMT (p<0.05), which was significantly correlated with TG level and systolic pressure (p<0.05). CONCLUSION: The weight loss achieved with bariatric surgery resulted in regression of C-IMT. This regression could be observed 6 months following surgery, with an additional benefit at 12 months. Also, this finding was correlated with a reduction in triglyceride levels and systolic blood pressure.

Angiotensin converting enzymes from human urine of mild hypertensive untreated patients resemble the N-terminal fragment of human angiotensin I-converting enzyme.

Angiotensin I-converting enzyme (ACE) activity was analyzed in human urine collected from mild hypertensive untreated patients. DEAE-cellulose chromatography using linear gradient elution revealed two forms of angiotensin I-converting enzyme, eluted in the conductivity of 0.75 and 1.25 mS. The fractions of each conductivity were pooled and submitted to direct gel filtration in an AcA-34 column, and the apparent molecular weights of urinary ACEs were estimated as 90 kDa (for ACE eluted in 0.75 mS) and 65 kDa (for ACE eluted in 1.25 mS). Both enzymes have a K(i) of the order of 10(-7) M for the specific inhibitors studied, and are able to hydrolyze luteinizing hormone-releasing hormone and N-acetyl-Ser-Asp-Lys-Pro as described for N-domain ACE. By Western blot analysis, both peaks were recognized by ACE-specific antibody Y4, confirming the molecular weight already described. A plate precipitation assay using monoclonal antibodies to the N-domain of ACE showed that both forms of ACE binds with all monoclonal antibodies to the active N-domain ACE, suggesting that these forms of human urine ACEs resemble the N-fragment of ACE. The HP2 ACE (65 kDa) is similar to low molecular weight (LMW) ACE from normal subjects, and the HP2 ACE (90 kDa) is different from high molecular weight (190 kDa) and LMW (65 kDa) normal ACEs. The 90 kDa ACE could have an important role in development of hypertension. It will be fundamental to elucidate the molecular mechanism responsible for the genesis of this isoform.

In vitro and in vivo evidence for an indirect mechanism mediating enhanced aldosterone secretion by metoclopramide.

Metoclopramide (MCP), a dopaminergic antagonist, increases the levels of plasma aldosterone in man and sheep. The present studies were designed to determine how MCP exerts this effect. In in vitro studies using collagenase-dispersed rabbit adrenal zona glomerulosa cells, MCP (10(-4) M) failed to increase aldosterone biosynthesis and had no effect on the dose-related increases induced by angiotensin II (AII) or ACTH. Dopamine (10(-5) M) had no effect on the AII- or ACTH-induced aldosterone responses of these cells. Aldosterone production of cells pretreated with dopamine and stimulated by AII or ACTH was unaltered by the addition of MCP. Bolus intraarterial injections of MCP increased plasma aldosterone significantly; however, this response was completely abolished by concomitant administration of L-dopa. Chronic im administration of MCP produced significant elevations of plasma aldosterone that were associated with increases in adrenal weight and in the adrenal weight to body weight ratio. Glomerulosa cells isolated from these adrenal glands had normal basal aldosterone production and exhibited enhanced sensitivity to AII but normal responses to ACTH. These results suggest that MCP is devoid of intrinsic steroidogenic activity and that it increases aldosterone production by antagonizing a tonic inhibitory dopaminergic mechanism that leads to enhanced aldosterone production. This enhanced aldosterone production is mediated in part by increased adrenocortical sensitivity to AII.

Long-term converting enzyme inhibition and sympathetic nerve function in hypertensive humans.

Orthostatic hypotension is uncommon during oral converting enzyme inhibition, even when combined with salt depletion. To assess the mechanisms responsible for the cardiovascular homeostasis in this condition, we studied the blood pressure (BP), heart rate (HR), total plasma catecholamines (CA), and plasma renin activity (PRA) responses after 20 minutes of 60 degrees head-up tilt in four groups of hypertensive patients. Group 1 included seven untreated patients; Group 2, eight patients on converting enzyme inhibitor (captopril) therapy; Group 3, six patients on diuretic therapy and Group 4, 15 patients on combined captopril and diuretic therapy. Long-term converting enzyme inhibition alone or in combination with diuretics resulted in reduction of mean arterial pressure (MAP) associated with a marked increase in PRA and fall in plasma aldosterone concentration (PAC). Pronounced increases in HR and plasma CA on tilt were observed in all groups. In Groups 1, 2, and 3, BP was maintained during tilt; in Group 4, three patients fainted between 5 and 15 minutes while the other 12 had a normal response to tilt. Plasma catecholamines increased more significantly after 15 and 20 minutes of tilt, more in Groups 3 and 4 than in Group 1, while no differences in HR response were observed among groups. Results suggest that sympathetic compensatory mechanisms are adequate in the majority of patients to maintain BP during converting enzyme inhibition even when combined with salt depletion. In a few who exhibited orthostatic hypotension, a vasovagal attack seemed to be responsible for bradycardia and fall in BP.

The role of vasopressin in blood pressure maintenance in diabetic orthostatic hypotension.

The purpose of these studies was to assess the role of vasopressin in maintaining supine and upright blood pressures in hypertensive diabetic subjects. Patients with (n = 6) or without (n = 10) evidence of autonomic insufficiency had blood pressure and heart rate monitored before and after receiving an intravenous injection of 0.5 mg of a V1 vasopressin inhibitor. None of the patients had supine changes in blood pressure or heart rate. However, upon assuming the erect position, the six patients with preexisting orthostatic hypotension had an average blood pressure fall of 44 mm Hg after vasopressin inhibition (as opposed to 20 mm Hg before), accompanied by a modest rise in heart rate of 20 beats/min. Those without autonomic dysfunction were separated into two subgroups. Four developed an average fall in orthostatic blood pressure of 18 mm Hg after vasopressin inhibition, whereas the remaining six had no change. There were no distinguishing hormonal characteristics (vasopressin, renin, and catecholamine levels) between the groups, but in the patients with autonomic dysfunction, the renin level failed to rise when upright. We conclude that vasopressin plays an important role in preventing or minimizing orthostatic hypotension in diabetic patients. Its pressor contribution is crucial in those with autonomic insufficiency and impaired renin and sympathetic responses, in whom the pressor effectiveness of vasopressin is greatly enhanced.

Hypokalemia, glucose intolerance, and hyperinsulinemia during diuretic therapy.

Hypokalemia and glucose intolerance may result from diuretic therapy. Increases in plasma insulin and glucose levels have been observed in thiazide-treated hypertensive patients and have been attributed to a diminished insulin sensitivity induced by diuretic therapy. To investigate the effects of hypokalemia on glucose tolerance and insulin secretion, we studied 21 essential and nine diabetic hypertensive patients after 4 weeks of placebo and after 4 weeks of chlorthalidone therapy (25 mg/day). Plasma glucose and insulin levels were measured for a 3-hour period after a 75-g glucose oral dose. Hypokalemia developed in seven of the essential hypertensive patients (HK group), whereas only one diabetic patient had decreased plasma potassium levels to below 3.5 meq/l. The results obtained in the HK group after chlorthalidone showed that plasma glucose and insulin values increased after the oral glucose load to levels significantly higher than those observed after placebo. In contrast, the patient who remained normokalemic after chlorthalidone did not show any change in plasma insulin and glucose levels during glucose tolerance testing. These results show that diuretic therapy may induce hyperglycemia and hyperinsulinemia and suggest that potassium depletion is involved in the increase in insulin resistance that has been demonstrated during thiazide therapy.

Familial hypertension and albuminuria in normotensive type I diabetic patients.

An inherited predisposition to hypertension may increase susceptibility to nephropathy in type I diabetes. We evaluated the influence of a family history of essential hypertension on albuminuria in normotensive, normoalbuminuric type I diabetic patients. Forty-two diabetics (12.9 +/- 2.04 years) were divided into three groups according to tertiles of albumin excretion rate (group 1, 1.27 +/- 0.35; group 2, 2.43 +/- 0.49; group 3, 6.37 +/- 3.43 micrograms/min; P < .001). Familial hypertension was considered to be present if the patient had one parent or grandparent on antihypertensive therapy. The three groups did not differ concerning age, diabetes duration, insulin requirement, body mass index, blood pressure, and urinary glucose excretion. Albumin excretion rate did not correlate with any parameter studied. The frequency of hypertension was significantly lower among the relatives of the patients from group 1 compared with those from groups 2 and 3 (28.6% versus 64.3% versus 78.6%, P < .03). Our data suggest that a familial antecedent of hypertension in normoalbuminuric type I diabetic patients is associated with a high normal albumin excretion rate not related to increases in blood pressure. Early changes in renal hemodynamics, seen in patients with a predisposition to hypertension, may contribute to increments in albuminuria even within the normal range.

Role of bradykinin in insulin sensitivity and blood pressure regulation during hyperinsulinemia.

The purpose of these experiments was to determine in normotensive rats the role of endogenous bradykinin, prostaglandins, and nitric oxide in glucose metabolism and blood pressure response to hyperinsulinemia. Normotensive Wistar rats were treated with two different bradykinin antagonists, indomethacin or N omega-nitro-L-arginine methyl ester, concurrently with a euglycemic clamp with insulin infusion rates of 3 or 6 mU/kg per minute. Glucose uptake, steady-state plasma insulin levels, and insulin sensitivity index were determined over 2 hours. Bradykinin inhibition dramatically reduced glucose uptake and insulin sensitivity index during both the lower and higher insulin infusion rates to 30% and 32%, respectively, of values observed in control rats. Inhibition of prostaglandins or nitric oxide did not alter glucose metabolism in these rats. Blood pressure remained unchanged in the control group throughout the clamp but increased significantly in rats submitted to inhibition of bradykinin, prostaglandins, or nitric oxide, suggesting that these vasodilator systems tend to counteract the hypertensive effect of hyperinsulinemia. The counterregulatory component attributable to bradykinin was about twice as great as that attributable to nitric oxide. These findings suggest that insulin infusion in normotensive Wistar rats fails to raise blood pressure because its effects are offset by mobilization of vasodilator mechanisms, such as bradykinin, prostaglandins, and nitric oxide. Bradykinin seems to play the most important homeostatic role under these conditions, because its inhibition significantly reduces insulin sensitivity and allows blood pressure to rise.

Serum insulin levels, 24-hour blood pressure profile, and left ventricular mass in nonobese hypertensive patients.

In essential hypertensive patients, considered to be insulin-resistant, a blunted decline in nocturnal blood pressure is associated with increased adrenergic tone and left ventricular mass. Since insulin stimulates the sympathetic system, we tested whether insulin resistance and insulinemia influence left ventricular mass and the 24-hour blood pressure profile. We studied 29 nonobese hypertensive patients with office diastolic pressure between 95 and 110 mm Hg and normal oral glucose tolerance test after a 4-month washout period. They were then assigned to M-mode echocardiographic evaluation and 24-hour ambulatory blood pressure monitoring. The glucose and insulin responses to a 75-g oral glucose load were compared with those obtained in 16 weight-matched normotensive control subjects. During the oral glucose tolerance test the hypertensive patients compared with control subjects presented higher levels of glucose at 60 minutes (138.7 +/- 30.3 versus 108.7 +/- 35.7 mg/dL; P < .05) and 90 minutes (114.0 +/- 23.8 versus 94.8 +/- 31.1 mg/dL; P < .05) and insulin at 60 minutes (287.1 +/- 259.4 versus 142.1 +/- 83.9 pmol/L; P < .05). However, peak insulin levels after glucose load did not correlate with ambulatory blood pressure values or left ventricular mass index. Left ventricular mass index showed significant correlation with mean sleeping systolic pressure (rs = 56, P < .05) and diurnal systolic pressure (rs = .37, P < .05) but not with mean diurnal or sleeping diastolic pressures. In conclusion, our results indicate that in nonobese hypertensive patients, insulin resistance does not have any influence on the 24-hour blood pressure profile or on left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium channel blockers as inhibitors of angiotensin I-converting enzyme.

Using ion-exchange chromatography of dialyzed human urine from healthy and hypertensive patients, we detected two peaks of angiotensin I-converting enzyme (ACE) activity on hippuryl-His-Leu eluted at ionic strengths of 0.7 (F1 peak) and 1.25 (F2 peak) mS. These hydrolytic activities decreased gradually in the urine of patients submitted to isradipine treatment, F2 and F1 disappearing after 12 and 24 hours, respectively. By Western blot analysis, the urine fractions corresponding to both peaks from healthy and untreated patients presenting ACE activity and from treated patients (24 hours) without this activity were recognized by an ACE-specific antibody. These results indicated that ACE was present but inhibited in the urine of isradipine-treated patients. In vitro assays with ACE isolated from human urine and guinea pig plasma demonstrated that the enzyme is inhibited by isradipine and other commercially available calcium channel blockers, such as felodipine, nifedipine, and verapamil. A noncompetitive inhibition was observed with all calcium channel blockers studied. In conclusion, these results suggest that besides the primary effect on calcium channels, the more commonly used calcium channel blockers are also ACE inhibitors. The development of efficient calcium channel blockers with higher ACE inhibitory activity could result in interesting bifunctional antihypertensive drugs.

Cardiovascular effects of a specific nonpeptide antagonist of substance P (NK-1) receptor in DOCA-salt hypertension.

The neurotransmitter substance P acts also as a potent vasodilator. Its participation in the pathogenesis of deoxycorticosterone acetate (DOCA)-salt hypertension was evaluated by an acute infusion of a newly synthesized, potent, specific nonpeptide antagonist of substance P at the NK-1 receptor, the agent CP 96,345. In conscious unrestrained rats, CP 96,345 induced significant and sustained increases in mean arterial pressure of DOCA-salt rats but only small, transient, and nonsignificant rises in blood pressure of sham-treated control rats. The rise in blood pressure was not accompanied by changes in heart rate. Maximal blood pressure increase in DOCA-salt rats was 31.7 +/- 14.8 mm Hg. In a second series of experiments, the hemodynamic effects of this antagonist were evaluated under anesthesia in both DOCA-salt and sham-treated control rats by the thermodilution method. During CP 96,345 infusion, sustained increases in cardiac index and stroke volume and decreases in total peripheral resistance were observed in both DOCA-salt and control rats. In DOCA-salt rats, cardiac index rose by 79.4%, while total peripheral resistance fell by 27.9% of the baseline values. In control rats, the changes were smaller (+27.2% and -22.5%, respectively). Stroke volume changed in parallel to cardiac output in both groups. The data suggest that acute blockade of NK-1 receptors increases blood pressure in DOCA-salt rats mainly by an increase in cardiac output. We conclude that endogenous substance P tends to counteract the DOCA-salt-induced elevation of blood pressure by modulating both cardiac output and peripheral resistance.

Role of substance P in blood pressure regulation in salt-dependent experimental hypertension.

The participation of substance P in the pathogenesis of five models of experimental hypertension, ie, DOCA-salt, subtotal nephrectomy, one-kidney-one clip renovascular, two-kidney-one clip renovascular, and spontaneous hypertension, was evaluated via an acute infusion of a newly synthesized potent, specific nonpeptide antagonist of substance P at the NK-1 receptor, the agent CP 96,345. In conscious unrestrained rats, CP 96,345 induced significant and sustained increases in mean arterial pressure of DOCA-salt, subtotal nephrectomy, and one-kidney-one clip renovascular hypertensive rats but only small and nonsignificant changes in blood pressure of two-kidney-one clip renovascular and spontaneously hypertensive rats. CP 96,345 had no effect on the blood pressure of sham-treated controls and Wistar-Kyoto rats. This NK-1 receptor antagonist did not significantly affect the heart rate of any experimental model studied. The data suggest that endogenous substance P may act as a partial counterregulatory mechanism against vasoconstriction in models of salt-dependent hypertension.

Hypertension and economic activities in São Paulo, Brazil.

A study of the prevalence of hypertension was undertaken among workers in 10 subsectors of the economy in São Paulo, a major urban-industrial area of Brazil. Included in the study were 5500 subjects 15-65 years of age, employed in 57 randomly selected firms. Hypertension rates (DBP greater than or equal to 90 mm Hg) were higher among males up to 44 years of age. There was a decreasing gradient from mild to moderate and severe forms in all groups. Severity tended to increase with age in all groups. Black males showed higher rates than whites (29.2% vs 16.7%, p less than 0.05), the excess being partially accounted for by moderate and severe forms (40% vs 20%). Subjects who overworked showed a trend toward higher hypertension rates. Higher rates in four subsectors (metallurgy, finance, transport, and journalism), aside from the distribution of known risk factors and job selection, may reflect a variety of work-related stressors.

Inadequate aldosterone response to hyperkalemia during angiotensin converting enzyme inhibition in chronic renal failure.

To assess the mechanism involved in hyperkalemia during angiotensin converting enzyme inhibition with captopril in chronic renal failure, captopril, 150 mg/day, was administered to 16 patients with hypertension with plasma creatinine levels between 1.6 and 12.4 mg/dl. After 4 weeks of therapy, plasma potassium levels increased from 3.9 +/- 0.1 to 5.5 +/- 0.2 mEq/L (P less than 0.001) and the final plasma potassium levels correlated with plasma creatinine levels (r = 0.67; P less than 0.01). In six patients with plasma creatinine levels greater than or equal to 3 mg/dl, aldosterone excretion decreased after 4 weeks of captopril, from 7.5 +/- 3.1 to 1.8 +/- 0.5 micrograms/24 hr, whereas plasma renin activity increased from 0.6 +/- 0.2 to 4.4 +/- 1.1 ng/ml/hr (P less than 0.05). This was associated with increases in plasma potassium levels from 3.9 +/- 0.2 to 5.4 +/- 0.4 mEq/L (P less than 0.005) and a significant reduction in fractional excretion of potassium from an average of 34% to 25%. No significant changes in plasma creatinine levels were observed during therapy. There was a significant positive correlation between aldosterone excretion and the potassium excretion fraction (r = 0.53; P less than 0.01). Increases in plasma potassium levels were not able to increase aldosterone excretion, although the greater the plasma potassium level attained, the smaller the reduction in aldosterone excretion (r = 0.47; P less than 0.05). Our results indicate that adequate aldosterone production is essential to preserve potassium homeostasis in chronic renal failure. Moreover, angiotensin II appears necessary for an adequate aldosterone response to potassium stimulation.

Peripheral dopaminergic blockade for the treatment of diabetic orthostatic hypotension.

This study was designed to evaluate the effects of domperidone, a peripheral dopaminergic antagonist, in diabetic patients with symptomatic orthostatic hypotension. Nine patients were admitted to the hospital, placed on a diet containing 150 mEq sodium, and studied for periods of 4 hours, on different days, in the following conditions: (1) supine position, (2) upright posture (UP), (3) UP after 10 mg domperidone, intravenously in bolus, and (4) UP after 3 days of domperidone, 30 mg orally. Before domperidone the mean blood pressure observed in supine position of 132 +/- 37/75 +/- 6 mm Hg fell to 75 +/- 22/57 +/- 13 mm Hg after 2 hours in UP. Acute domperidone did not change the blood pressure response to UP. After 3 days of oral domperidone and in UP for 2 hours, the mean blood pressure value of 89 +/- 21/61 +/- 8 mm Hg was higher than that before domperidone (p less than 0.05), with relief of symptoms in all patients. This blood pressure response to UP has been maintained in six patients who completed 6 months of therapy. No differences were observed in plasma renin activity, aldosterone, sodium, and potassium and in 4-hour urinary excretion of aldosterone, epinephrine, norepinephrine, and dopamine, determined during the UP tests. Administration of domperidone for 3 days reduced the falls in creatinine clearance and the urinary excretion of sodium and potassium induced by UP but did not alter the blood pressure and aldosterone dose-response curves to angiotensin II. Although the mechanism of action is not defined, it is concluded that domperidone is effective for the treatment of orthostatic hypotension in patients with diabetes.

Acute hemodynamic and humoral effects of metoclopramide on blood pressure control improvement in subjects with diabetic orthostatic hypotension.

Metoclopramide (MCP), a dopaminergic antagonist, is effective in postural hypotension, but the mechanisms of action have not been well defined. We studied responses of mean arterial pressure (MAP), heart rate, cardiac output (CO), and total peripheral resistance (TPR) after 5 min of increasing degrees of head tilt (15 degrees to 90 degrees) before and after MCP (20 mg IV) in seven subjects with diabetic postural hypotension. Plasma renin activity (PRA) and plasma aldosterone levels (PA) were determined at each degree of tilt; responses to the cold pressor test were also assessed before and after MCP. Before MCP, the maximal degree of tilt tolerated was 75 degrees, while after MCP four subjects were able to support 90 degrees tilt. At 45 degrees tilt, the decreases in MAP were smaller after than before MCP (-7.6 +/- 3.3 and -28.1 +/- 8.5 mm Hg; means +/- SE). This was associated with responses of TPR to tilt after (from 18.6 +/- 2.6 to 24.0 +/- 3.9 arbitrary units [AU]) but not before (from 22.9 +/- 4.0 to 25.6 +/- 4.5 AU) MCP. Reductions in CO were of the same order before and after MCP. PRA responded to tilt better after than before MCP. Supine PA levels increased with MCP (delta PA = 5.4 +/- 0.7 ng/dl), but its response to tilt was unaltered. There were significant rises in MAP and HR during the cold pressor test after but not before MCP. Our data suggest that vasoconstriction is the main mechanism of MCP improvement in blood pressure response to an orthostatic stimulus in diabetic postural hypotension, possibly because of its antidopaminergic property.

Preserved semantic access in neglect dyslexia.

The aim of this study was to investigate the preservation of semantic access in patients with severe neglect dyslexia for words and non-words. Patients were given the following tasks: (1) reading aloud letter strings (first basic reading task), (2) making semantic decisions (categorial and inferential judgements), (3) making semantic decisions and reading the letter strings immediately afterwards (semantic-reading tasks), (4) reading letter strings again (final basic reading tasks) and (5) auditory control tasks. Of 23 patients with visual neglect, four showed neglect dyslexia for both words and non-words. Of these four patients, three showed a performance in the semantic tasks that was as good as in the auditory condition. Moreover, the reading of the patients improved dramatically in the semantic-reading tasks but this was not maintained in the final basic reading task. Non-words showed only a minor improvement. Findings are discussed in terms of an interaction between the attentional system and the different reading routes, and provide evidence that semantic routes are less affected by neglect.

Angiotensin-converting enzyme (ACE) inhibition. Therapeutic option for diabetic hypertensive patients.

When choosing antihypertensive agents for the treatment of diabetic patients with hypertension, it is necessary to consider the individual characteristics of these patients. In this respect, angiotensin-converting enzyme (ACE) inhibitors constitute an attractive option for diabetic patients. The effects of enalapril alone for 16 weeks in 23 non-insulin-dependent diabetic (NIDD) patients and in 10 non-diabetic patients with mild to moderate essential hypertension (EH) [diastolic blood pressure greater than 95 mm Hg and less than 115 mm Hg] were evaluated. Similar reductions in both systolic and diastolic blood pressure were observed in 17 NIDD patients (from 155 +/- 18/100 +/-11 mm Hg to 128 +/- 12/82 +/- 8 mm Hg, respectively) and in 6 EH patients (from 155 +/- 21/100 +/- 6 mm Hg to 125 +/- 20/84 +/- 8 mm Hg, respectively) who achieved and maintained blood pressure control (diastolic blood pressure less than 90 mm Hg) for 16 weeks. In 4 NIDD and 4 EH patients blood pressure was not controlled. Two NIDD patients discontinued the medication, one because of symptomatic postural hypotension and the other, who had a plasma creatinine level of 1.8 mg/dl, because of hyperkalaemia (K = 6.1 mEq/L). In the responders, enalapril did not alter glucose tolerance, plasma or urinary excretion of creatinine, potassium, sodium and aldosterone. Plasma renin activity increased in the NIDD group only. In 11 patients (6 NIDD and 5 EH), the elevated protein or albumin excretions decreased. It is concluded that enalapril is a good therapeutic option for NIDD patients with hypertension.

Hypertension. A major public health problem in Brazil.

Data collected from various geographical areas show that hypertension is a major public health problem in Brazil. Hypertension is estimated to occur in over 8 million Brazilians and cardiovascular disease-related mortality figures, to which hypertension is a major contributor, increased from 11.8% of the total mortality rate in 1930 to 30.8% in 1980. Costs involved in the treatment of hypertensive patients are very high since hypertension was among the 3 most frequent clinical diagnoses in outpatient visits in 1985. Hypertension is also a major cause of temporary or permanent work incapacitation among Brazilians and data from São Paulo show that hypertension is very common among workers. Finally, demographic tendencies in São Paulo indicate that older age groups have increased in the general population during the past 2 decades. These data, when taken altogether, indicate that hypertension is a major public health problem in Brazil.

Hypertension and diabetes. Clinical problems.

The choice of an appropriate antihypertensive agent and the hazards of postural hypotension are common problems faced in the treatment of diabetic hypertensive patients. The results of 3 studies addressing these problems are described in this report. In the first study, indoramin, an alpha-blocking agent, was administered to patients with non-insulin-dependent diabetes and mild to moderate hypertension. Blood pressure control was achieved in 57% of patients with mild, and in none with moderate hypertension. The blood glucose and insulin responses to an oral 50g glucose loading, as well as the blood concentrations of HbA1 did not change during therapy. Seven patients were excluded because of side effects. In 4 of them postural hypotension was observed. In the second study, the effects of angiotensin-converting enzyme (ACE) inhibitors, administered to patients with non-insulin-dependent diabetes and mild to moderate hypertension, were evaluated. Blood pressure control was achieved in 78% of the patients on captopril (n = 14) and in 74% of patients on enalapril therapy (n = 23). Symptomatic postural hypotension (n = 2) and hyperkalaemia (n = 2) were observed with both drugs. Significant reductions in 24-hour urinary protein or albumin excretion were detected in 12 patients on enalapril therapy. No changes in 2-hour postprandial blood glucose and HbA1 levels were observed during therapy with ACE inhibitors. In the third study, dopaminergic antagonist agents were evaluated in diabetic patients with orthostatic hypotension. In 7 patients metoclopramide (20mg intravenously) reduced the fall in mean arterial pressure induced by upright tilt.(ABSTRACT TRUNCATED AT 250 WORDS)