Dietary salt restriction is a recommended adjunct with antihypertensive therapy. There may be racial differences in blood pressure response to salt restriction while on antihypertensive therapy. We performed a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial (black, n=96; Hispanic, n=63; white, n=232). Participants were initially preselected for stage I to III hypertension and then further selected for salt sensitivity (> or = 5 mm Hg increase in diastolic blood pressure after 3 weeks of low salt [< or = 88 mmol/d Na+] and high salt [>190 mmol/d Na+] diet). We compared the antihypertensive effect of an angiotensin-converting enzyme inhibitor (enalapril 5 or 20 mg BID) or a calcium channel antagonist (isradipine 5 or 10 mg BID) during alternating periods of high and low salt intake. The main outcome measure was blood pressure change and absolute blood pressure level achieved with therapy. During the high salt diet (314.7+/-107.5 mmol/d urinary Na+) there was greater downward change in blood pressure with both enalapril and isradipine compared with the low salt diet (90.1+/-50.8 mmol/d Na+); however, the absolute blood pressure achieved in all races was consistently lower on a low salt diet for both agents. Black, white, and Hispanic isradipine-treated salt-sensitive hypertensives demonstrated a smaller difference between high and low salt diets (black, -3.6/-1.6 mmHg; white, -6.2/-3.9 mmHg; Hispanic, -8.1/-5.3 mm Hg) than did enalapril-treated patients (black, -9.0/-5.3 mm Hg; white, -11.8/-7.0 mm Hg; Hispanic, -11.1/-5.6 mm Hg). On the low salt diet, blacks, whites, and Hispanics had similar blood pressure control with enalapril and isradipine. On the high salt diet, blacks had better blood pressure control with isradipine than with enalapril, whereas there was no difference in the blood pressure control in whites and Hispanics treated with either drug. Dietary salt reduction helps reduce blood pressure in salt-sensitive hypertensive blacks, whites, and Hispanics treated with enalapril or isradipine. These data demonstrate that controlling for salt sensitivity diminishes race-related differences in antihypertensive activity.
were smallest at 4 and greatest at 8 atm absolute. In IX-sectioned rats the rates of rise of VT at 4, 6 and 8 atm absolute and off at 4 atm absolute were similar to those of intact rats. At 6 atm absolute and even more so at 8 atm absolute, however, f decreased. Hence the slope of FE in IX-sectioned compared with intact rats was similar at 4 atm absolute but smaller at 6 and 8 atm absolute. In fact at 8 atm absolute F'E remained constant in IX-sectioned rats.3. Since the slope of VE versus time in intact rats was steeper the greater the pressure and since the removal of carotid bodies in IX-sectioned rats reduced the G'E slope at 6 and 8 atm absolute, the stimulus to the hyperventilation induced by o.h.p. cannot be an accumulation of CO2 in the brain resulting from the lack Of 02 desaturation of haemoglobin. This theory would predict that PE should be identical at all pressures above 3-5 atm absolute.4. The findings in the IX-sectioned rats indicate a major contribution of the carotid bodies to the f increase in o.h.p. They may be stimulated by a histotoxic hypoxia induced by early 02 poisoning. Since the VT increase on exposure to o.h.p.was both large and fairly similar in intact and IX-sectioned rats, it is suggested that a large part ofthe VT increase was caused by stimulation ofthe central chemoreceptors by lactic acidosis induced by an o.h.p.-induced histotoxic hypoxia of the brain.
ObjectivesPermethrin use has been associated with an increased risk of multiple myeloma (MM) among pesticide applicators. However, the biological plausibility and mechanisms underlying this association are not fully understood. The aim of this study was to assess whether exposure to permethrin is related to haematological alterations among occupationally exposed pesticide applicators.MethodsWe conducted a longitudinal study among 33 pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture study comparing haematological parameters in the offseason with the day after permethrin exposure and, for 27 participants, approximately 3 weeks postexposure. Complete blood counts with white blood cell differential and lymphocyte subsets were measured at each visit. Multivariate linear mixed effects models were used to assess the relationship between natural log-transformed haematological parameters and exposure to permethrin.ResultsThe adjusted geometric mean immature granulocyte count was elevated among pesticide applicators following permethrin exposure compared with their offseason levels (37% increase, 95% CI 6% to 76%). Modest but statistically significant (p<0.05) alterations in red blood cell (RBC) parameters (eg, decreased RBC count and haemoglobin and increased mean corpuscular volume and RBC distribution width-SD) were also observed the day after permethrin use compared with offseason levels; decreases in RBC count and haemoglobin and increases in RBC distribution width-SD persisted approximately 3 weeks after permethrin use.ConclusionsAltered haematological parameters could be indicative of disrupted haematopoiesis, providing insights into the biological plausibility of the observed association between permethrin use and MM risk among pesticide applicators.
The 24-h integrated plasma concentration of aldosterone (IC-ALDO), PRA (IC-PRA), and cortisol (IC-F) were measured in 34 male patients with uncomplicated mild essential hypertension and 15 matched normal controls using a portable 24-h continuous nonthrombogenic blood withdrawal system. The hypertensive were subsequently given 0.5 mg dexamethasone three times per day, resulting in suppression of their urinary excretion of 17-hydroxycorticosteroids and free cortisol. The diastolic blood pressure of the hypertensives fell during adrenal suppression from 104 +/- 5 to 96 +/- 8 mm Hg (mean +/- 1 SD; P less than 0.0001). The systolic pressure fell from 150 +/- 16 to 148 +/- 17 (P greater than 0.01). Baseline values for IC-F, IC-ALDO, and IC-PRA were similar in hypertensive subjects and normal controls. After treatment with dexamethasone for 8 weeks, IC-F in the hypertensives decreased from 7.8 +/- 2.1 to 0.7 +/- 0.6 microgram/dl (P less than 0.0001). There was no associated change in IC-ALDO or IC-PRA. Thus, the fall in diastolic blood pressure in response to dexamethasone was associated with suppression of IC-F, without demonstrable changes in other endocrine or biochemical factors measured.
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