CHANGE IN BLOOD PRESSURE IN RELATION TO CHANGE IN NUTRIENTS EFFECTED BY MANIPULATION OF DIETARY SODIUM AND POTASSIUM

1. As part of a study investigating the effect of dietary alterations of sodium and potassium intake on blood pressure, the changes in nutrients that occurred with dietary intervention were determined. 2. Mild hypertensive subjects were randomized to one of four dietary intervention groups: control; high potassium; low sodium; low sodium, high potassium. The changes in nutrients in each diet group were assessed by dietary history and five repeat 24 h dietary recalls. Assessment was validated by measurement of urinary nitrogen excretion and urinary electrolytes. 3. The three dietary intervention groups experienced a fall in blood pressure (systolic: 4.4 +/- 1.0 mmHg, P less than 0.005; diastolic: 3.3 +/- 0.7 mmHg, P less than 0.001), greater than that observed in the control group. 4. The only significant dietary change across all diet groups was a reduction in the dietary sodium/potassium ratio, which was significantly less than that of the control group. The only other nutrient to differ from the control in all groups was fat intake, which was reduced. 5. In the control group there was a small but significant decrease in energy, fibre, protein, carbohydrate, potassium and magnesium intake. In the high potassium group there was a significant increase in fibre, carbohydrate, potassium, magnesium, and a decrease in calcium intake. In the low sodium group there was a decrease in energy intake with a subsequent reduction in all nutrients except alcohol. In the low sodium, high potassium group there was a significant reduction in dietary sodium and protein and an increase in fibre, carbohydrate, potassium and magnesium. 6. The reduction of the dietary sodium/potassium ratio correlated with a reduction in the urinary sodium/potassium ratio. This was the best predictor for change in diastolic pressure in all groups, suggesting that reduction in the sodium/potassium ratio contributed to the fall in blood pressure. 7. Reduction of sodium intake and increase in potassium intake by dietary means caused a reduction in blood pressure which does not appear to be due to alteration of other measured dietary constituents.     

EFFECTS OF DIETARY SODIUM RESTRICTION AND FISH OIL SUPPLEMENTS ON BLOOD PRESSURE IN THE ELDERLY

1. The effects on blood pressure of dietary fish oil, sodium restriction and a combination of both strategies were examined in a short-term dietary intervention study of 50 healthy elderly subjects (average age 67 years) with mean initial systolic and diastolic blood pressures of 133 and 77 mmHg, respectively. 2. Subjects were allocated to one of four treatment groups: fish oil with normal sodium, fish oil with low sodium, sunflower oil with normal sodium and sunflower oil with low sodium for 4 weeks. They then crossed over to the alternative sodium treatment for a further 4 weeks whilst remaining on the same oil. 3. The combination of fish oil supplementation with dietary sodium restriction caused significant reductions of blood pressure in the first 4 weeks: systolic blood pressure (SBP) fell by 8.9 mmHg, mean arterial pressure (MAP) by 7.4 mmHg and diastolic blood pressure (DBP) by 6.0 mmHg. 4. Fish oil enhanced the effect of sodium restriction on blood pressure. In the crossover protocol, a change in sodium excretion of 92 mmol/day was accompanied by changes of 6.4, 3.3 and 2.2 mmHg for SBP, MAP and DBP, respectively, in the subjects taking fish oil. However in those taking sunflower oil, blood pressure did not change significantly. 5. The results indicate beneficial interactive effect of dietary fish oil and sodium intake on blood pressure.     

Felodipine extended release in mild to moderate hypertension

A multi-centre study was carried out to examine the antihypertensive effect and adverse event profile of felodipine in an extended-release (ER) formulation given once daily as monotherapy. Doses of 5 mg, 10 mg or 20 mg felodipine ER were compared with placebo in 183 patients with mild or moderate hypertension. All antihypertensive medication was discontinued on entering a 4-week placebo run-in period. If, at the end of the run-in period, supine diastolic blood pressure was in the range greater than 95 less than 120 mmHg, patients were randomly allocated to double-blind treatment with felodipine, 5 mg, 10 mg or 20 mg, or placebo, to be taken once daily for 4 weeks. Supine and standing blood pressure, heart rate and body weight were measured every 2 weeks during the trial. Assessments were made 24 hours after intake of the study drug. Adverse events were recorded at each review. Over the 4-week treatment period, a dose-related decrease in supine diastolic blood pressure was observed, this reduction occurring already during the first 2 weeks of active treatment. In the placebo group and the felodipine 5 mg, 10 mg and 20 mg groups, supine blood pressure (systolic/diastolic) decreased by 7/6 mmHg, 9/8 mmHg, 12/10 mmHg and 14/11 mmHg, respectively. Supine diastolic blood pressure reduction in the felodipine 10 mg group and both systolic and diastolic blood pressure reductions in the 20 mg group were significantly greater than with placebo. Standing diastolic blood pressure reduction was significantly greater in all three dose groups on felodipine compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood pressure and alpha-vascular reactivity in hypertensive rats treated with amlodipine and dietary Ca

It has been suggested that the combination of dietary Ca and Ca2+ channel antagonists could have a synergic antihypertensive effect. In this study, 3-week-old male spontaneously hypertensive rats (SHR) were randomized into four groups of animals. Two of these groups were fed on a normal Ca diet (Ca 1%) and the other two groups were fed on a Ca-enriched diet (Ca 2.5%). One of the groups fed on each diet also received amlodipine (1 mg/kg/day) in their drinking water. Systolic and diastolic arterial blood pressure were measured weekly in the rats, from the 6th week of life until the 25th week of life, by the tail-cuff method, and we also calculated the corresponding pulse pressure values (systolic blood pressure-diastolic blood pressure). Determination of plasma Ca levels by colourimetric methods, and measurement in pithed rats of the pressor responses to the alpha-adrenoceptor agonists methoxamine and B-HT 920 (5-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d)-acepin-dihydrochloride, talixepole) were also performed using 16- and 23-week-old animals from the different groups. The Ca-enriched diet decreased systolic and diastolic blood pressure in SHR. Almodipine also decreased systolic and diastolic blood pressure in SHR, and this drug intensified the antihypertensive effect of the Ca 2.5% diet in the SHR between weeks 13 and 18. Nevertheless, in the 19- to 25-week-old SHR amlodipine antagonized the effect of dietary Ca on arterial blood pressure. A decrease in the pulse pressure was seen only in the 15- to 20-week-old SHR which had been simultaneously treated with dietary Ca and amlodipine. All the treatments used increased calcaemia, and the highest plasma Ca levels were obtained in the animals which had received the combined treatment with Ca and amlodipine. The responses to methoxamine and to B-HT 920 in the pithed 16-week-old SHR were similar in the four groups of animals. The responses to these agonists in the pithed 23-week-old SHR fed on the Ca-enriched diet were smaller than the corresponding responses in 23-week-old SHR of the untreated group. By contrast, the responses to these agonists were slightly higher in the pithed 23-week-old SHR which were treated with amlodipine than in the pithed 23-week-old SHR in the untreated group. Moreover, amlodipine partially reversed the effect of dietary Ca on alpha-vascular reactivity. According to our results, it would seem inadvisable to use dietary Ca with a Ca2+ channel antagonist with the aim of controlling arterial blood pressure.     

Double-blind clinical evaluation of dimetophrine in chronically reduced arterial tension

Thirty in-patients with chronically reduced arterial blood pressure and relevant subjective symptoms were treated over a 15-day period with oral doses of either 400 mg dimetophrine twice daily or placebo, according to a prospective, randomized, double-blind design. Systolic and diastolic blood pressures and heart rate were monitored at 5-day interval: subjective specific symptoms (scored 0 to 3 in order of increasing severity), haematology and haematochemistry were recorded before and after treatment. Both systolic and diastolic blood pressures increased significantly after dimetophrine all through the observation period. After 5 days, systolic blood pressure had already reached significantly higher values in comparison with the placebo-treated group, as did diastolic blood pressure by the 10th day. Overall, during the observation period, an increase from 82.7 +/- 1.0 to 112.3 +/- 2.1 mmHg was observed in systolic and from 54.3 +/- 1.3 to 62.7 +/- 1.4 mmHg in diastolic blood pressure with dimetophrine, whereas with placebo, systolic blood pressure increased from 80.4 +/- 1.5 to 93.7 +/- 2.9 mmHg and diastolic blood pressure remained unchanged (53.3 +/- 1.4 mmHg). Concomitantly, heart rate decreased significantly with dimetophrine from 88.1 +/- 2.5 to 77.2 +/- 1.4 beats/min, whereas it remained almost unchanged with placebo (from 83.9 +/- 2.5 to 80.0 +/- 1.9 beats/min). The associated symptoms (asthenia, paleness, drowsiness, fatigue, sweating, vertigo and headache) were largely relieved by dimetophrine (70.0% decrease) but not by placebo (37.4%). All symptoms except drowsiness and vertigo were reduced to a significantly larger extent with dimetophrine than with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetic and pharmacodynamic modelling of arterial haemodynamic effects of terazosin in healthy volunteers

OBJECTIVE: This study aimed to investigate, in healthy volunteers, the relationship between the plasma concentrations of the alpha(1)-adrenoceptor antagonist terazosin and its effects on arterial blood pressure after a single oral administration of terazosin 2 mg. M ethods: Twenty-four healthy volunteers participated in this study. Pharmacokinetic and pharmacodynamic modeling were performed subject by subject. First, plasma concentrations were fitted according to a one-compartment model with first-order absorption and monoexponential elimination. Then the maximum drug-induced decrease (E(max)) effect compartment-model was developed to describe the pharmacodynamic relationships between systolic and diastolic blood pressure and plasma concentrations using the pharmacokinetic parameters that were previously estimated. RESULTS: For systolic blood pressure, E(max) was 29.9 +/- 10.6 mmHg. The corresponding value for decrease in diastolic blood pressure was 39.7 +/- 8.6 mmHg. The effects of terazosin on systolic and diastolic blood pressure could be quantified by an inhibitory E(max) effect compartment model. The obtained first-order rate constant values (0.40 +/- 0.006 h(-)(1) for systolic blood pressure and 0.47 +/- 0.012 h(-)(1) for diastolic blood pressure) were consistent with the rapid development of pharmacological effect. EC(50) (concentration of terazosin that induces an effect at 50% of E(max) values) values were similar for systolic (29.9 +/- 4.3 microg/L) and diastolic (28.7 +/- 4.0 microg/L) blood pressure. A decrease in diastolic blood pressure was the most sensitive response after oral administration of a single dose of terazosin. CONCLUSION: The direct haemodynamic effects of terazosin can be characterized by an E(max) effect compartment model.     

Effects of prazosin and alphamethyldopa on blood lipids and lipoproteins in hypertensive patients

Summary The effects of prazosin and alphamethyldopa on blood lipids and lipoproteins were assessed in 20 patients with mild or moderate arterial hypertension. Parameters measured included serum cholesterol (CHO), triglycerides (TG), high density lipoprotein-cholesterol (HDL-CHO), insulin (I), glucose (G), and non-esterified fatty acids (NEFA). Prazosin — 4 mg/day for 6 weeks in hydrochlorothiazide-treated patients lowered blood pressure by 18.6/17.2 (systolic/diastolic pressure) mmHg. There was a significant decrease in CHO (–5.8%), in I (–16.5%), and in NEFA (–3.0%), and a significant increase in HDL-CHO (+15.5%). Alphamethyldopa 250–750 mg/day for 6 weeks in hydrochlorothiazide-treated patients lowered blood pressure by 18.8/14.6 (systolic/diastolic pressure) mmHg, accompanied by a non-significant decrease in CHO and TG, and significant increases in HDL-CHO (+10.3%), G (+8.5%) and NEFA (+6.4%). Thus, prazosin appears to have a more beneficial effect on blood lipids and lipoproteins than alphamethyldopa.     

The efficacy of hydrochlorothiazide, timolol and enalapril in Ethiopians with essential hypertension.

A double-blind trial of hydrochlorothiazide, timolol and enalapril was carried out in Ethiopians with essential hypertension at the Tikur Anbessa Hospital, Addis Abeba, between 1987 and 1990. Patients with a supine diastolic blood pleasure of 95-120 mmHg after a washout period of 2 weeks were randomized to receive hydrochlorothiazide 25 mg daily, timolol 10 mg daily or enalapril 10 mg daily. Doses were doubled at 4 weeks if the diastolic blood pressure remained above 95 mmHg. At the end of 8 weeks of treatment, there were 9 patients taking hydrochlorothiazide, 10 patients taking timolol and 7 patients taking enalapril. Hydrochlorothiazide significantly lowered both systolic and diastolic blood pressure at 4 and 8 weeks compared with pre-treatment levels. Timolol and enalapril did not significantly lower the systolic blood pressure, but each lowered the diastolic blood pressure at 4 weeks and 8 weeks respectively. More patients on hydrochlorothiazide attained a diastolic blood pressure of less than 90 mmHg while less patients required doubling of dosage compared to timolol and enalapril. It is concluded that Ethiopian hypertensives may respond better to diuretics than to beta-blockers or angiotensin converting enzyme inhibitors, as found in other black populations.     

奥美沙坦酯片治疗轻中度原发性高血压的疗效和安全性

目的评价国产奥美沙坦酯片治疗轻中度原发性高血压的疗效和安全性。方法用随机双盲双模拟多中心活性药对照的试验设计,符合入选条件的221例轻中度原发性高血压患者随机分为奥美沙坦酯组和氯沙坦组,治疗8周,观察2组治疗前后的血压、心率、心电图和血尿实验室检查的变化。动态血压用开放试验方法,分别在安慰剂末期和治疗期结束时(未停药),做24h动态血压监测。结果奥美沙坦组与氯沙坦组比较,平均坐位收缩压和舒张压降低程度都有显著性差异,分别为17.22vs11.02mmHg,(P<0.01);13.41vs11.18mmHg(P<0.05)。奥美沙坦组降压总有效率为82.41%;每日1次服用奥美沙坦酯片作用可持续24h,药物降低收缩压和舒张压的谷峰比值均>50%。2组药物不良反应发生率分别为3.5%,5.4%,2组比较无显著性差别。结论国产奥美沙坦酯片治疗轻中度原发性高血压患者,能24h平稳降压,谷峰比满意,且耐受性较好。     

EFFECT OF SODIUM DEPLETION ON PRESSOR RESPONSIVENESS IN ACTH-INDUCED HYPERTENSION IN MAN

1. Pressor responsiveness to angiotensin II (AII) and phenylephrine (PHE) was measured before and after 5 days of ACTH (1 mg i.m. daily) in six normal men maintained on low sodium diet (15 mmol daily). 2. ACTH caused a significant increase in systolic blood pressure of 9 mmHg. 3. There was no change in pressor responsiveness to AII with ACTH. 4. ACTH increased pressor responsiveness to PHE for both systolic and diastolic blood pressure, with a fall in the threshold for response from 0.9 to 0.6 micrograms/kg per min. 5. Increased pressor sensitivity to catecholamines during ACTH administration in man is not sodium-dependent.