Salt supresses baseline muscle sympathetic nerve activity in salt-sensitive and salt-resistant hypertensives.

The objective of our study was to evaluate the role of the baroreflex control of peripheral sympathetic nervous system on the increase of muscle sympathetic nerve activity (MSNA) in salt-sensitive (SS) and salt-resistant (SR) hypertensives under low salt diet. In phase I mild-to-moderate hypertensive patients (n=5) received three diet periods: a first regular salt (RS1), a low salt (LS=20 meq Na+/day), followed by a second regular salt diet (RS2) with a 7-day duration of each. At the end of each period, sympathetic and heart rate baroreflex control were recorded. Baseline MSNA varied (P<0.005) from 18+/-8 (RS1) to 32+/-9 (LS) and to 14+/-9 (RS2) bursts per minute (bpm). In phase II additional patients (n=6) were included to have baseline MSNA, sympathetic and heart rate baroreflex control evaluated at the end of the LS and RS2. For all patients (n=11), there was a significant decrease of MSNA from 36+/-4 to 20+/-8 bpm on day 7 of LS to RS2 (P<0.05). The response of MSNA to a salt restriction was similar for SS and SR patients, who showed a change from 32+/-6 to 18+/-11 and from 36+/-9 to 17+/-7 bpm for SS and SR on day 7 of LS and RS2 diets, respectively (P<0.05). MSNA baroreflex gain was similar during phenylephrine infusions at day 7 of LS and RS2 (5.1+/-1.6 and 6.1+/-2.9 bpm/mmHg), but it was reduced under LS during sodium nitroprusside infusion (19.5+/-4.9 vs 8.9+/-0.7 bpm/mmHg) (P<0.05) for the whole group. Baroreflex control of MSNA was also similar during phenylephrine infusions under LS and RS2 diets for SS (4.0+/-0.9 and 3.3+/-0.2 bpm/mmHg) and for SR patients (10.1+/-2.5 and 5.6+/-1.5 bpm/mmHg). During nitroprusside infusion, baroreflex gain was significantly greater under RS2 for SR patients (19.5+/-2.6 bpm/mmHg) when compared to LS (11.2+/-5.2 bpm/mmHg) and the same significant difference was observed among SS patients (14.4+/-4.7 and 9.1+/-3.6 bpm/mmHg under RS2 and LS diets, respectively). There was no difference in heart rate baroreflex gain between LS and RS2 diets. Data support the hypotheses that (1) sodium supresses baseline MSNA in SS and SR hypertensives and (2) sodium restriction may impair baroreflex control of MSNA in SR and SS mild-to-moderate hypertensive patients during blood pressure reductions.

Mild chronic renal insufficiency induces sympathetic overactivity.

The objectives of this study were to evaluate baseline sympathetic nerve activity as well as the mechanisms of sympathetic overactivity in mild chronic renal insufficiency hypertension. Seven hypertensives with mild renal insufficiency, seven hypertensives with normal renal function and seven normotensives, age and weight-matched were studied on one session to evaluate baseline muscle sympathetic nerve activity measured in the peroneal nerve. The mild renal insufficiency hypertensives and the hypertensives with normal renal function were also studied to evaluate arterial baroreflex control of muscle sympathetic nerve activity assessed by increasing and decreasing blood pressure through continuous infusion of phenylephrine and sodium nitroprusside respectively. Baseline muscle sympathetic nerve activity was significantly higher in mild renal insufficiency hypertensives (34 bursts/min) when compared to hypertensives with normal renal function (24 bursts/min) and to normotensives (16 bursts/min). Baroreflex control of muscle sympathetic nerve activity was (in absolute values) 15.2 in hypertensives with normal renal function vs 2.6 in mild renal insufficiency hypertensives (P < 0.05) during phenylephrine and 6.3 vs 8.2 during nitroprusside infusions. Mild renal insufficiency hypertensives showed sympathetic overactivity when compared to hypertensives with normal renal function and to normotensives. This finding demonstrates that elevated sympathetic activity may be precociously detected in renal insufficiency. Baroreflex gain to phenylephrine was blunted in mild renal insufficiency hypertensives when compared to hypertensives with normal renal function, suggesting that bradycardic response in mild renal insufficiency is blunted.

[Single daily dose of verapamil (COER-24 180/24 mg) in mild and moderate hypertension evaluated by ambulatory blood pressure monitoring]. / Verapamil COER-24 180/240 mg na hipertensão arterial leve a moderada em dose única diária avaliado pela monitorização ambulatorial da pressão arterial.

OBJECTIVE: To evaluate the anti-hypertensive effect of verapamil COER-24 180/240 mg in a single dose at bedtime as single therapy in mild to moderate hypertensives. METHODS: A multicentric, open, placebo controlled study of 81 hypertensive patients older than 20 years-old followed to 8 weeks. Blood pressure was measured in doctor's office and by 24 h ambulatory monitoring (ABPM). RESULTS: We observed a decreased in systolic and diastolic blood pressure in doctor's office at 4th and 8th weeks. ABPM showed that both systolic, diastolic and mean blood pressure, heart rate and the mean 24-hour blood pressure load decreased after the 8-week treatment. In addition, there was a reduction of the double-product, especially in the morning and 68% of the patients didn't have any adverse events. CONCLUSION: The therapy verapamil COER-24 180/240 mg in a single dose is useful for mild and moderate hypertensive patients, with significant pressure decrease in both office blood pressure measurements and in the ABPM/24 hours, as well as showing good tolerability.

[Captopril combined with hydrochlorothiazide in mild and moderate hypertension. A Brazilian multicenter study]. / Captopril associado à hidroclorotiazida no tratamento da hipertensão leve e moderada. Estudo multicêntrico brasileiro.

PURPOSE: To evaluate the effectiveness and tolerance of the association of captopril 50 mg and hydrochlorithiazide 25 mg in hypertensive patients with diastolic pressure between 95 and 115 mmHg. METHODS: An open, multicenter and non-comparative study was performed. After 2 weeks of placebo, the patients received 1/2 tablet of drug association. Patients were evaluated after 4, 8 and 12 weeks, and those who had diastolic pressure > 90 mmHg after 8 weeks of therapy received 1 tablet/day. RESULTS: The results of 433 patients were analyzed: 47 +/- 10 years old, 30% female, 76% white. Initial systolic and diastolic pressures were 156 +/- 16 and 103 +/- 11 mmHg and after 14 days of placebo were 156 +/- 15 and 103 +/- 9 mmHg (p > 0.05). Systolic/diastolic pressure after 4, 8 and 12 weeks of treatment reduced progressively (p < 0.05) to 143 +/- 14/95 +/- 11, 140 +/- 13/91 +/- 9 and 134 +/- 11/86 +/- 8 mmHg. Blood pressure control was observed in 45, 67 and 88% (p < 0.05) of patients after 4, 8 and 12 weeks. Cough was the most important symptom, registered in 7% of patients under placebo and 12% in patients under treatment. The tolerance was considered good for 98% of patients. CONCLUSION: The association of captopril with hydrochlorothiazide is effective with good tolerance, being indicated as a once a day monotherapy for mild and moderate hypertension.

Effect of long-term blood pressure control on salt sensitivity.

The objective of this study was to reevaluate salt sensitivity (SENS) after a period of antihypertensive treatment (AT). SENS was measured in ten patients, before and after 18 +/- 6 months on AT. The average for all mean blood pressures (MBP) measured during AT was used as an index of blood pressure (BP) control. After at least eight weeks on placebo only, all patients were submitted to an ad libitum diet (ALD), low salt diet (LSD), and high salt diet (HSD) during one week each. SENS was considered as the percent change of the MBP between the seventh day of LSD and HSD. Weight, BP, and daily urinary Na+ and K+ excretion (mean of seven days) on ALD were the same in the first (F) and second (S) evaluation. SENS did not significantly change from the F and S measurement. An inverse correlation was obtained between individual SENS difference and the average mean blood pressure (AMBP) (r = -0.85, p = 0.0018). In conclusion, patients who showed greater decreases in SENS were the ones with the best BP control.

[Treatment of mild and moderate hypertension with diltiazem 240mg. Brazilian multicenter trial]. / Tratamento da hipertensão arterial leve e moderada com diltiazem 240mg. Estudo multicêntrico brasileiro.

PURPOSE: The efficacy and safety of diltiazen 240mg was evaluated in essential hypertensive patients with diastolic pressure in the range of 95 to 115 mmHg. METHODS: In an open, non-comparative multicenter trial 2.165 hypertensives had the supine and orthostatic arterial blood pressure measured before, after 14 days with non pharmacologic therapy and after 40 days taking diltiazen 240mg/day. Also, the serum levels of lipids, glucose and electrolytes were measured before and after the use of the active drug. RESULTS: The systolic arterial pressure in the first day was 166 +/- 18mmHg, in the 14th day was 155 +/- 20mmHg; and, in the 54th day was 141 +/- 14mmHg (p < 0.05). Also, supine and orthostatic diastolic blood pressure was lower in the 14th and in the 54th days when compared to baseline (p < 0.05). Cholesterol, triglycerides, urea and uric acid levels decreased significantly (p < 0.05) during treatment. CONCLUSION: This study demonstrates that diltiazem 240mg/day for the treatment of hypertension is well tolerated, efficient and shows no metabolic undesirable effects.

[Evaluation of efficacy of the enalapril-hydrochlorothiazide combination by ambulatory blood pressure monitoring in essential hypertensive patients]. / Avaliação da eficácia da associação enalapril-hidroclorotiazida através da monitorização ambulatorial da pressão arterial em hipertensos essenciais.

PURPOSE: Evaluation the 24 hours efficacy of once daily enalapril plus hydrochlorothiazide association by ambulatory blood pressure monitoring. METHODS: Thirty-nine essential hypertensive patients (3 male, 36 female; 31 white, 8 non-white; mean age 46,7 years old) with the criteria, after wash-out period, of more than 40% of diurnal diastolic blood pressure measurements above 90mmHg by ambulatory blood pressure monitoring, were allocated for treatment during 8 weeks with once daily administration of enalapril (20mg) plus hydrochlorothiazide (12.5mg) association. RESULTS: After wash-out period, 82 and 42%, respectively, diurnal and nocturnal systolic blood pressure measurements were above 140mmHG; while diastolic values were 79 and 26% above 90mmHg. After 8 weeks of treatment there was a significant reduction in both systolic and diastolic pressure loads, either on nocturnal or diurnal periods; 26 and 5.3% of systolic values were still above 140mmHg and, 31.5 and 7.9% of diastolic measurements were above 90mmHg. Despite the significant fall on blood pressure there was not alteration in heart rate. CONCLUSION: The association of the angiotensin converting enzyme inhibitor, enalapril, plus a diuretic, hydrochlorothiazide, promoted a significant reduction on pressure load and did not interfere with the circadian rhythm of 24 hours blood pressure. These results may indicate that the association as suitable as one of the first choices for treating mild and moderate hypertensive patients.

Adult respiratory distress syndrome: evidence of early fibrogenesis and absence of glucocorticoid receptors.

In five lung biopsies from patients who developed the clinical picture of Adult Respiratory Distress Syndrome (ARDS) after cardiopulmonary bypass the pulmonary alterations were studied morphologically and glucocorticoid receptors determined. The time between cardiac surgery and pulmonary biopsy was 4-7 days. The results showed severe pulmonary lesions, with marked endothelial damage and active collagen secretion in the pulmonary interstitium, along the capillary bed. The glucocorticoid receptor level of the lungs with ARDS was 4.7 +/- 7.04 fmol/mg protein (control 4.28 +/- 4.32 fmol/mg protein). The results indicate that the process of collagen secretion may begin in the early phase of ARDS and that the benefits of glucocorticoid therapy in the management of ARDS should be reassessed.