Treatment of essential hypertension with felodipine in combination with a diuretic

Summary In a double-blind cross-over study, the effect on blood pressure (BP), heart rate (HR) and plasma noradrenaline concentration (pNA) of placebo or felodipine given in addition to hydrochlorothiazide was studied in 12 male patients with essential hypertension, not satisfactorily controlled with the diuretic alone. The first dose of felodipine decreased BP and increased HR for about 6 h. After 4 weeks of treatment with felodipine, BP was reduced for 24 h, whereas HR was only transiently increased. The elimination half-life of felodipine was about 23 h. The plasma noradrenaline concentration increased after felodipine and serum uric acid decreased. Side-effects were few and usually mild.     

Comparison of the effects of felodipine and cilazapril on exercise performance in patients with mild to moderate hypertension. A crossover study

This double-blind crossover study was designed to compare the effects of felodipine and cilazapril on exercise performance in hypertensive patients. After a 2-week placebo run-in period, 40 patients with mild to moderate hypertension were randomized into two parallel groups to receive either felodipine (10 mg) or cilazapril (5 mg) for 4 weeks. After another 2-week washout period, treatments were then crossed over for a further 4-week study period. All patients were given an extensive rest and exercise evaluation at the end of the placebo period. Extensive rest and exercise evaluations were repeated after a 4-week treatment period and again after the second washout period and after the second 4-week treatment period. Before each exercise test, epinephrine, norepinephrine and dopamine plasma levels and plasma renin activity were measured. Two groups were similar at baseline for systolic and diastolic blood pressure and heart rate as well as for laboratory and hormonal variables and duration of exercise test. At the end of treatment diastolic blood pressure was significantly reduced in the felodipine group (p = 0.019). Duration of exercise test was longer than at baseline (p = 0.031) in the felodipine group. Plasma dopamine levels were significantly increased in the cilazapril group. Plasma renin activity significantly increased in the felodipine group. In conclusion, our data show that the two drugs have the same effectiveness in resting conditions but that felodipine is more effective in lowering maximum exercise diastolic blood pressure and in improving exercise time with an double product increase (not significant); it has no statistically significant effect on maximal exercise systolic 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)     

Felodipine ER formulation in the treatment of mild hypertension: efficacy and tolerability vs placebo.

1. Felodipine is a new calcium-antagonist dihydropyridine derivative with a high degree of selectivity for smooth muscle of arteriolar resistance vessels, as opposed to cardiac cells. 2. In this double-blind, cross-over study the antihypertensive efficacy and tolerability of the new extended release (ER) formulation of felodipine 10 mg, once daily, in patients with mild essential hypertension was evaluated. After a 4-week single-blind placebo period 28 patients (15 males; mean age 48 +/- 12 years) were randomized to receive felodipine 10 mg ER once daily or placebo for 4 weeks and the alternative treatment for a further 4 weeks. Supine blood pressure and heart rate were measured in the out-patients department every 2 weeks, 22-24 h after the last drug administration. 3. Felodipine 10 mg ER induced a significant reduction in blood pressure in comparison with placebo (from 149 +/- 16/97 +/- 6 to 140 +/- 12/89 +/- 6 mm Hg). Heart rate remained unchanged. Seven patients dropped-out; five during felodipine ER administration and two during placebo. 4. A once daily dose of felodipine ER significantly reduces blood pressure in mild hypertensive patients 22-24 h after administration. It is well tolerated and the adverse events are related to its pharmacodynamic effects.     

Felodipine in hypertension

Summary Felodipine, a selective arteriolar dilator, was given to 13 hypertensive patients to assess its hypotensive effects and duration of action. Nine patients were treated with 5 mg three times a day and 4 with 10 mg three times a day.Mean blood pressures fell with both treatment regimens: 5 mg placebo 170/103 mmHg; 5 mg felodipine 148/91 mmHg; 10 mg placebo 154/93 mmHg; 10 mg felodipine 137/82 mmHg.Heart rates increased as blood pressures fell with both treatments. However, in the patients given 5 mg three times a day this effect was less noticeable after successive doses.Plasma concentrations of noradrenaline, both resting and tilted, increased after felodipine. There was a negative correlation between the fall in blood pressure and the increase in noradrenaline, suggesting that those patients with good baroreceptor reflexes were better able to counteract the effects of vasodilatation.Four of the nine patients treated with 5 mg felodipine three times a day experienced mild and transient adverse effects. Of the four patients treated with 10 mg three times a day, three experienced moderate to severe headache, and for this reason recruitment into this group was stopped.Felodipine at a divided daily dose of 15 mg effectively lowered blood pressure.     

Cross-over comparison of nifedipine Oros and felodipine extended release with blind 24 h ambulatory blood pressure assessments

1. The aim of the present study was to compare the efficacy of nifedipine Oros and felodipine extended release (ER) in controlling 24 h ambulatory blood pressures (ABP) in hypertensive patients. 2. The study was a randomized cross-over design with a 2 week open placebo run-in phase and two observer-blind treatment periods. 3. Subjects were males and females, aged between 18 and 65 years, suffering from mild to moderate essential hypertension with a sitting mean diastolic blood pressure (DBP) within the range of 95-114 mmHg. Twenty-three subjects were randomized to treatment; 15 patients completed the study. 4. Treatment intervention was 2 weeks of placebo followed by either 30 mg nifedipine OROS once daily or 5 mg felodipine ER once daily for 6 weeks, which was titrated up to 60 mg nifedipine OROS daily or 10 mg felodipine ER daily after 2 weeks of treatment on the lower doses if the DBP was > 90 mmHg. The main outcome measure was 24 h ABP after 6 weeks of active treatment, evaluated by an independent observer blinded as to treatment allocation. 5. Compared with placebo, mean (+/- SD) 24 h DBP was reduced by 6.2 +/- 6.8 and 5.2 +/- 5.1 mmHg after nifedipine and felodipine, respectively. The 24 h mean systolic blood pressure (SBP) fell by 11.8 +/- 10.9 and 10.1 +/- 8.2 mmHg for nifedipine and felodipine, respectively, compared with placebo. There were no significant differences between the two active treatments in the reduction of DBP or SBP during the 24 h period, daytime or night-time. 6. Similar antihypertensive effects are achieved with nifedipine Oros and felodipine ER when doses are individually titrated, with no significant differences between the two treatments.     

Effect of indomethacin on the pharmacokinetics and pharmacodynamics of felodipine.

1. We studied the effects of pre-treatment with oral indomethacin (25 mg four times daily for 3 days) on the pharmacokinetics, haemodynamics and diuretic properties of oral felodipine (10 mg single dose) in 12 healthy male volunteers using a placebo controlled double-blind four-way crossover protocol. 2. Felodipine with or without indomethacin pretreatment reduced standing diastolic blood pressure (P less than 0.001) at 0.5 to 3.0 h after dosing compared with placebo or indomethacin alone. Systolic blood pressures during indomethacin treatment alone were consistently higher than the other three treatment groups (P less than 0.01), presumably due to sodium and fluid retention. 3. Felodipine and felodipine plus indomethacin produced significantly greater excretion of urine and urinary sodium, but not of urinary potassium or creatinine when compared with placebo (P less than 0.01) over an 8 h period. 4. The pharmacokinetic parameters of felodipine (Cmax, tmax, t1/2 and AUC), the concentration-response curves for blood pressure lowering effects, the reflex tachycardia, diuretic properties and side-effects profile of felodipine were not significantly altered by indomethacin pretreatment in normal volunteers.     

Beta-adrenergic receptors and reflex tachycardia after single and repeated felodipine administration in essential hypertension.

To verify the possible contribution of beta-adrenergic receptor down-regulation to the reversal of reflex tachycardia during chronic treatment with a dihydropyridine calcium antagonist, 11 hypertensive patients were studied with noninvasive blood pressure (BP) and heart rate (HR) monitoring after a placebo period, and on the first and seventh day of felodipine administration, 5 mg twice daily. Plasma catecholamines and neutrophil beta-adrenergic receptors were measured on the first and seventh day of treatment, immediately before and 2 h after drug administration. The first administration of felodipine was followed by a significant drop in BP (peak reduction in mean BP 24 +/- 7 mm Hg), lasting 6 h and mirrored by reflex tachycardia (peak increase in HR 14 +/- 9 beats/min). On the morning of the seventh day, 12 h after the previous felodipine administration, mean BP (MBP) was 16 mm Hg lower than on the last placebo day, while HR was unchanged. The next administration of felodipine was followed by a smaller drop in BP (MBP - 15 +/- 7 mm Hg; NS vs. placebo), while reflex tachycardia was the same as after acute felodipine (HR 13 +/- 8 beats/min; p less than 0.05 vs. placebo, NS vs. acute administration). Plasma noradrenaline concentration increased after both acute and chronic administration (p less than 0.0001), and preadministration values were highest on day 7 (p less than 0.05). Neutrophil beta-adrenergic receptor density and affinity did not change either acutely or chronically. This study gives both indirect and direct evidence that beta-adrenoceptor down-regulation does not occur during repeated felodipine administration in hypertension. Reflex tachycardia is not abolished, but is reset to lower BP levels.     

Catecholamines, renin-angiotensin-aldosterone, and cardiovascular response during exercise following acute and long-term calcium antagonism with felodipine in essential hypertension

Studies were performed in nine patients with essential hypertension to explore the effect of the calcium antagonist felodipine on the exercise-induced responses of the sympathetic and renin-angiotensin-aldosterone systems as well as of blood pressure and heart rate. The patients were subjected to an individually graded submaximal work test (bicycling) after administration of placebo and a single dose of felodipine (10 mg) in a double-blind design and following long-term (8 weeks) felodipine treatment (10 mg twice daily). After a single dose of felodipine sitting preexercise blood pressure was decreased, whereas heart rate, plasma noradrenaline, adrenaline, renin activity, and angiotensin II increased. After long-term felodipine treatment blood pressure was reduced, heart rate was unchanged, and plasma noradrenaline and renin activity increased. The exercise-induced increases in plasma catecholamines, renin activity, angiotensin II, aldosterone, blood pressure, and heart rate were similar after acute and long-term felodipine administration as compared with placebo. In conclusion, acute and long-term felodipine treatment influences neither reflex activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system nor the cardiovascular responses to physical exercise in patients with essential hypertension.     

Plasma concentration-effect relationships of intravenous and extended-release oral felodipine in hypertensive patients.

Felodipine, a dihydropyridine calcium antagonist, was given double-blind in a crossover design comparing once-daily doses of 20 mg felodipine extended-release (ER) tablets with placebo in 12 hypertensive patients. A 2-h intravenous infusion was given after a placebo washout. After oral felodipine, blood pressure (BP) was significantly lower than after placebo, both after the first dose and after 2 weeks of treatment. Supine BP 24 h after the first dose of placebo and felodipine was 159/97 and 153/92 mm Hg (p less than 0.01/0.05), respectively. Corresponding BPs at 2 weeks were 158/99 and 144/89 mm Hg (p less than 0.01/0.01). Approximately 75% of the maximal and 60% of the trough effect at steady state were obtained already after the first dose. The plasma concentration (CpF) vs. time curve after felodipine ER was relatively flat. After oral felodipine, a linear correlation was found between BP reduction and logarithmic CpF. After intravenous administration, CpF correlated well with a hyperbolic function. These data indicate that there is an almost linear relation between BP reduction and log CpF in the range from 2-20 nmol/L, and that little additional effect is to be expected above approximately 20 nmol/L. No hysteresis was found for the relationship between CpF and BP reduction. The absolute bioavailability of felodipine ER was 22%.     

Twenty-four hour blood pressure profiles in hypertensive patients following various formulations and dosage regimens of felodipine

Summary The blood pressure lowering capacity of felodipine administered either as extended release tablets once or twice daily or as plain tablets twice daily has been compared in a double-blind, three-way cross-over study in 16 hypertensive patients. All the patients were on long-term treatment with 10 or 20 mg felodipine daily and other antihypertensive therapy (mainly beta-blockers) was allowed if it was kept unchanged. Non-invasive blood pressure and heart rate recordings were obtained throughout 24 hour periods using an Accutracker ambulatory system.The 24 h mean systolic and diastolic blood pressures after extended release tablets o.m. did not differ significantly from those after extended release tablets b.d. or plain tablets b.d. There was a tendency for the extended release tablets given o.m. to reduce blood pressure somewhat more in the morning, and for the extended release tablets b.d. to reduce blood pressure more during the night than the other treatments. Mean 24 h heart rate after all treatments was comparable. Manual recordings confirmed these results. Blood pressure was well-controlled throughout the 24 h period by all three treatments.The extended release tablets tended to give less extreme plasma concentrations of felodipine. This may be of value for patients with adverse vasodilator effects. For a majority of hypertensive patients the adequacy of blood pressure control and the simplicity of once daily dosing will favour the extended release tablet given once daily.This study was supported by a grant from the Swedish Heart and Lung Foundation     

Effects of calcium antagonism on the resting and exercise-stimulated renin-aldosterone axis

The effect of short-term calcium antagonism with felodipine on blood pressure and on some biochemical plasma variables such as catecholamines, renin and aldosterone was studied in 10 normal volunteers at rest and during incremental bicycle exercise. At rest, diastolic blood pressure was slightly decreased during felodipine, whereas systolic pressure and heart rate were not significantly changed. The plasma noradrenaline concentration and plasma renin activity were increased during felodipine treatment; the plasma adrenaline and aldosterone concentrations on the contrary, were not significantly changed. The rises in plasma renin activity, plasma aldosterone and plasma adrenaline and noradrenaline concentrations produced by exercise were not significantly affected by felodipine. The plasma calcium concentration was significantly higher during felodipine treatment than during placebo and this was accompanied by an increased urinary calcium excretion. It is concluded that the rise in plasma renin activity during calcium antagonism with felodipine is not accompanied by a significant increase in plasma aldosterone. Furthermore, the present data suggest that, at least during exercise, calcium antagonism does not interfere with the mechanisms underlying the exercise-induced activation of renin and aldosterone release.     

Antihypertensive effect of felodipine or hydralazine when added to beta-blocker therapy

In a double-blind randomized study, hydralazine (n = 59) or the new dihydropyridine calcium antagonist felodipine (n = 61) was added to previous treatment with beta-adrenoceptor blocking agents in a group of 120 patients with essential hypertension. Active treatment with either hydralazine or felodipine was given for 8 weeks after a 4-week placebo run-in period, at the end of which all patients had supine diastolic blood pressures greater than 95 mm Hg. Assessment of the results according to the intention to treat principle showed that felodipine was significantly more effective than hydralazine at the doses employed, reducing systolic blood pressure 10-19 mm Hg more than hydralazine and reducing diastolic blood pressure 5-11 mm Hg more than hydralazine (95% confidence intervals). The number of patients complaining of side effects, the number of complaints, and the number of patients that had to be withdrawn from treatment were numerically higher during treatment with hydralazine than with felodipine, but these differences were not statistically significant. Against this background it is concluded that felodipine is superior to hydralazine when added to an antihypertensive regimen consisting of beta-adrenoceptor blocking agents.     

Natriuretic and diuretic effects of felodipine and hydrochlorothiazide after single and repeated doses

The effects of the calcium antagonist, felodipine, and hydrochlorothiazide (HCTZ) on natriuresis/diuresis and blood pressure were evaluated in 12 healthy subjects. The investigation was designed as a double-blind, three-way, randomised, crossover study, and all comparisons were performed against placebo. Urine volume, urine sodium excretion, heart rate and blood pressure were measured after a single dose of felodipine 10 mg, HCTZ 12.5 mg or placebo as well as during steady-state conditions (6 days of treatment with felodipine 10 mg b.i.d., HCTZ 12.5 mg b.i.d. or placebo).A significant increase in natriuresis was seen in the first 4 h after a single dose of felodipine and HCTZ, and the effect of felodipine was approximately 40% that of HCTZ. When the entire 24-h period after a single dose was studied, there was a significant increase in natriuresis after HCTZ, but not after felodipine, compared with placebo.A significant increase in diuresis was found in the first 4 h after a single dose of HCTZ, but not after felodipine, compared with placebo.Under steady-state conditions, there were no statistically significant differences between felodipine and placebo or HCTZ and placebo when the 24-h period, as a whole was considered.Potassium excretion was not affected by any of the drugs. Felodipine caused a significant decrease in diastolic blood pressure in this study. This was not the case for HCTZ or placebo.     

Dissociated effects of nicardipine on vascular tone and insulin secretion

Because Ca2+ antagonists may alter glucose homeostasis by blocking calcium entry into pancreatic beta-cells, this risk was evaluated for nicardipine, a new dihydropyridine derivative with vasodilatory effects. It was tested in vitro for its vascular and insulinotropic effects on isolated perfused rat pancreases. In vivo, an oral glucose tolerance test (OGTT) was conducted, and blood pressure was recorded in eight hypertensive patients with glucose intolerance who were given 90 mg/day nicardipine for 2 weeks in a single-blind placebo-controlled study. In vitro, insulin output was inhibited by 10(-4) M nicardipine but not by 10(-8) M and 10(-6) M, whereas significant changes in intrapancreatic perfusate flow indicated that vascular resistance was similarly reduced by all three concentrations. In vivo, blood pressure diminished significantly after nicardipine, but neither glucose tolerance nor insulin release was further impaired during OGTT. From these in vitro data and this short-term clinical follow-up, it is suggested that nicardipine reduces vascular tone at doses lower than those required to inhibit insulin secretion.     

Lercanidipine in type II diabetic patients with mild to moderate arterial hypertension

This study evaluates the effects of lercanidipine antihypertensive treatment on glucose homeostasis in patients with type II diabetes mellitus with mild to moderate hypertension. Forty patients were enrolled. After a 2-week wash-out period, they were randomly allocated to receive in double-blind manner either 10 mg or 20 mg in single daily administration for 8 weeks. Nonresponding patients after the initial 4 weeks, were titrated up to 20 mg and 30 mg lercanidipine, respectively. At the end of the double-blind treatment, all patients entered in single-blind 4 weeks placebo follow-up. Systolic and diastolic blood pressure significantly decreased in both groups of patients after 4 weeks of treatment, and decreased further during the following 4 weeks. In both groups, progressive and significant decrease in fasting blood glucose, glycosylated hemoglobin and area under the curve of the oral glucose tolerance test were detected during lercanidipine treatment. Similarly, a decrease in serum fructosamine values were also observed. All variables returned to towards baseline values during the placebo follow-up period. Adverse events (headache and mild asthenia) were limited to two patients and resolved spontaneously. These data indicate that lercanidipine is effective in lowering high blood pressure in hypertensive patients with type II diabetes mellitus and does not exert negative effects on glucose homeostasis.     

Effects of a new long-acting beta-blocker bopindolol (LT 31-200) on blood pressure,plasma catecholamines,renin and cholesterol in patients with arterial hypertension

Summary Bopindolol (LT 31-200), a new, long-acting, non-selective beta-blocker, was given as monotherapy to 13 patients, 12 with essential hypertension and 1 with renovascular hypertension. After a placebo period of 4–6 weeks, bopindolol was given once daily, starting with 1 mg and subsequently increasing at two-weekly intervals to 2 and 4 mg once daily until a diastolic blood pressure⩽90 mmHg was achieved. The effective dose was continued for 12 weeks. In 10 patients plasma levels of renin, noradrenaline, adrenaline and cholesterol were measured during placebo and after 3 months of therapy. Blood pressure and heart rate were lowered significantly during bopindolol treatment. The mean effective dose was 2.2 mg per day. In 10/13 patients a diastolic blood pressure⩽90 mmHg was achieved. Side effects were minimal. Changes in plasma noradrenaline and adrenaline were small and not significant, but renin and cholesterol were significantly reduced. Thus, LT 31-200 is an effective and well tolerated beta-blocker when given in a once daily dosage.     

Influence of hydrochlorothiazide on the plasma levels of triglycerides, total cholesterol and HDL-cholesterol in patients with essential hypertension.

The influence of hydrochlorothiazide (HCT) treatment on the plasma levels of triglycerides, total cholesterol and high density lipoprotein cholesterol (HDL-cholesterol) was studied in 10 patients with essential hypertension. After a placebo period of 4 weeks, 50 mg HCT twice daily was given for a period of 9 months, followed by a second placebo period of 4 weeks. Triglycerides, total cholesterol and HDL-cholesterol were determined at the end of both placebo periods and after 1, 3, 6 and 9 months of HCT. For the whole group, there were no significant changes in triglycerides or HDL-cholesterol, whereas total cholesterol significantly increased during HCT. In 6 patients, plasma triglycerides were higher during HCT as compared to both placebo periods. In only 4 patients did HDL-cholesterol increase during HCT. Changes in triglycerides, total cholesterol and HDL-cholesterol were not related and no correlation was found with changes in blood pressure, body weight or serum potassium. In conclusion, this study confirms a possible adverse effect of diuretic treatment on plasma lipids, which should be considered when determining therapeutic regimens for hypertension.     

The acute haemodynamic and renal effects of oral felodipine and ramipril in healthy subjects

Summary The aim of the present investigation was to compare the acute haemodynamic and renal effects of the calcium antagonist felodipine with the ACE inhibitor ramipril and with placebo.Single oral doses of felodipine 5 and 20 mg, ramipril 2.5 and 10 mg, and placebo were given to ten healthy subjects in a double-blind cross-over study. Blood pressure, heart rate, forearm blood flow (FBF), forearm vascular resistance (FVR), renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR), filtration fraction (FF), diuresis, and sodium excretion were recorded for 4.75 h after administration.Felodipine 20 mg caused a significant fall in diastolic blood pressure, maximal 12 % compared with placebo, while there were no significant effects of felodipine 5 mg or the two doses of ramipril. Heart rate increased significantly after both doses of felodipine, maximal 28% after the 20 mg dose. There was also a small but significant increase in heart rate of 12% after ramipril 2.5 mg. FVR fell significantly after both doses of felodipine, maximal 38 % after the 20 mg dose. There were no significant changes in FVR after any of the ramipril doses. Both doses of felodipine and both doses of ramipril caused significant reductions in RVR. Maximal reduction, 33 %, was found after felodipine 20 mg. There were no significant changes in GFR or FF with either drug. Felodipine caused a significant increase in natriuresis, maximal 129% while ramipril did not.     

Influence of hydrochlorothiazide on the plasma levels of triglycerides,total cholesterol and HDL-cholesterol in patients with essential hypertension

Summary

The influence of hydrochlorothiazide (HCT) treatment on the plasma levels of triglycerides, total cholesterol and high density lipoprotein cholesterol (HDL-cholesterol) was studied in lo patients with essential hypertension. After a placebo period of 4 weeks, 50?mg HCT twice daily was given for a period of 9 months, followed by a second placebo period of 4 weeks. Triglycerides, total cholesterol and HDL-cholesterol were determined at the end of both placebo periods and after 1, 3, 6 and 9 months of HCT. For the whole group, there were no significant changes in triglycerides or HDL-cholesterol, whereas total cholesterol significantly increased during HCT. In 6 patients, plasma triglycerides were higher during HCT as compared to both placebo periods. In only 4 patients did HDL-cholesterol increase during HCT. Changes in triglycerides, total cholesterol and HDL-cholesterol were not related and no correlation was found with changes in blood pressure, body weight or serum potassium. In conclusion, this study confirms a possible adverse effect of diuretic treatment on plasma lipids, which should be considered when determining therapeutic regimens for hypertension.