Treatment of arterial hypertension with tienilic acid,a new diuretic with uricosuric properties.

Tienilic acid--2,3-dichloro-4-(2-thienyl-carbonyl)phenoxyacetic acid--is a new diuretic with uricosuric properties. Nineteen patients with moderate arterial hypertension were treated for 5 consecutive weeks in a randomized fashion in a double-blind study with either tienilic acid or hydrochlorothiazide. Blood pressure was significantly reduced and to the same degree with both drugs. In 7 of the 11 patients receiving tienilic acid the daily dose was increased from 250 to 500 mg after 2 weeks, and in 2 of the 8 patients taking hydrochlorothiazide the daily dose was increased from 50 to 100 mg. Because of the potent uricosuric action of tienilic acid the mean serum urate concentration decreased from 6.3 to 3.3 mg/dL in the patients taking the drug. In contrast, the patients receiving hydrochlorothiazide the mean serum urate concentration increased from 6.1 to 7.8 mg/dL. Moderate hypokalemia of almost identical degree (mean serum potassium values 3.6 and 3.5 mmol/L) and mild metabolic alkalosis were observed in both groups. Tienilic acid had a marked hypocalciuric effect, which was of the same magnitude as the observed with hydrochlorothiazide. During the 5 weeks of treatment no significant change in renal or liver function was observed in either group. There were no hematologic complications and the drug was remarkably well tolerated. Tienilic acid, because of its unique character as a diuretic, hypouricemic and antihypertensive agent, should become the preferred drug for the treatment of arterial hypertension.     

Verapamil versus hydrochlorothiazide in the treatment of hypertension: results of long term double blind comparative trial. Verapamil versus Diuretic (VERDI) Trial Research Group.

OBJECTIVE--To compare the efficacy and tolerability of hydrochlorothiazide, sustained release verapamil, and their combination in patients with mild to moderate hypertension. DESIGN--Randomised multicentre trial of 48 weeks'' duration with a double blind comparison of hydrochlorothiazide and verapamil followed by an open trial of combined treatment for patients not achieving the target diastolic blood pressure (less than 90 mm Hg) during treatment with a single drug. SETTING--Outpatient departments in 10 clinics and 10 private practices of general practitioners or internists. PATIENTS--369 Hypertensive patients with a diastolic blood pressure of 95-120 mm Hg during a placebo run in period of two weeks. INTERVENTIONS--Initial treatment consisted of 12.5 mg hydrochlorothiazide (n = 187) or 120 mg sustained release verapamil (n = 182) once daily (regimen I). If the target diastolic blood pressure of less than 90 mm Hg was not achieved within four weeks doses were increased to 25 mg hydrochlorothiazide or 240 mg verapamil once (regimen II) and twice daily (regimen III). Patients not achieving target blood pressure were given the combination of hydrochlorothiazide and verapamil--that is, 25 and 240 mg once (regimen IV) and twice daily (regimen V). MAIN OUTCOME MEASURE--Blood pressure determined with a device permitting automatic repeated measurements with printouts. RESULTS--After eight weeks of treatment with a single drug 76 out of 178 (43%) and 101 out of 175 (58%) patients achieved the target blood pressure with hydrochlorothiazide and verapamil, respectively. During follow up until 48 weeks patients treated with verapamil reached the target blood pressure more often and at lower doses and were less likely to switch to combination treatment than patients randomised to hydrochlorothiazide treatment. Adding verapamil to hydrochlorothiazide was more effective than the addition of hydrochlorothiazide to verapamil. At the end of the study 42 out of 169 (25%) and 73 out of 163 (45%) patients initially randomised to hydrochlorothiazide and verapamil, respectively, were at target blood pressure without combination treatment. After adding verapamil to hydrochlorothiazide or hydrochlorothiazide to verapamil an additional 58 (34%) and 29 (18%) patients reached the target blood pressure, respectively. Altogether 92 out of 332 (28%) patients failed to achieve target blood pressure with regimen V. There were four, 10, seven, and seven withdrawals due to possible adverse effects to treatment with hydrochlorothiazide, verapamil, combining verapamil with hydrochlorothiazide, and combining hydrochlorothiazide with verapamil, respectively. CONCLUSIONS--In doses currently used in antihypertensive treatment verapamil was more effective than hydrochlorothiazide as a single agent and in combination in mild to moderate hypertension, whereas withdrawal rates caused by side effects possibly related to treatment were similar.     

Captopril in essential hypertension; contrasting effects of adding hydrochlorothiazide or propranolol.

Twenty-four patients with moderate to severe hypertension were treated for four weeks with captopril, an oral inhibitor of angiotensin-converting enzyme. The fall in blood pressure with captopril alone correlated with pretreatment plasma renin activity. The effect of adding either hydrochlorothiazide or propranolol to the captopril treatment was then studied. The addition of hydrochlorothiazide to captopril produced a dose-dependent fall in blood pressure. At the higher dose of the diuretic this fall in blood pressure correlated with weight loss, suggesting that when the diuretic-induced compensatory rise in angiotensin II is prevented by captopril the fall in blood pressure becomes dependent on loss of sodium and water. In contrast, the addition of propranolol to captopril produced no further fall in blood pressure, suggesting that inhibition of angiotensin-converting enzyme prevents the blood pressure lowering effect of propranolol. This may have implications for the mechanism whereby beta-blockers alone lower blood pressure. These contrasting effects of hydrochlorothiazide and propranolol in the presence of captopril indicate that in patients whose hypertension is not controlled by captopril alone the addition of increasing doses of diuretic is likely to control the blood pressure. The addition of a beta-blocker, however, is less likely to be effective.     

Hypokalemia during the treatment of arterial hypertension with diuretics.

In a study of 50 patients with uncomplicated arterial hypertension the administration of hydrochlorothiazide, 50 to 100 mg daily or every other day, with or without reserpine, 0.25 mg daily, resulted in a fall in the mean blood pressure from 182/113 to 144/92 mm Hg. The mean duration of therapy was 19 months. The mean serum potassium concentration was 4.3 mmol/l before the onset of therapy. It fell during the first 6 weeks of treatment, but seldom below 3.5 mmol/l, then rose gradually and spontaneously to 4.1 mmol/l after 19 months of therapy. All the patients remained asymptomatic. These findings bring into question the routine use of potassium supplements or a potassium-sparing diuretic, such as spironolactone or triamterene, during the treatment of hypertension with diuretics such as the thiazides. The use of potassium supplements or a potassium-sparing agent may induce hyperkalemia in spite of the simultaneous administration of a diuretic that acts more proximally. Since hyperkalemia is potentially lethal, the serum potassium concentration should be carefully monitored in any patient receiving potassium supplements or a potassium-sparing agent.     

Lack of effect of beta-blocker on flat dose response to thiazide in hypertension: efficacy of low dose thiazide combined with beta-blocker.

Increasing the dose of a thiazide diuretic used alone in patients with essential hypertension has little further effect on blood pressure but increases the deleterious metabolic consequences of the diuretic. The effect of a beta-blocker on this flat dose response is not known. In two randomised crossover studies the effect of 12.5 mg, 25 mg, and 50 mg hydrochlorothiazide combined with 400 mg acebutolol was assessed. The mean fall in supine blood pressure was about 15% and was the same whatever dose of thiazide was used with the beta-blocker. As the dose of hydrochlorothiazide was increased, however, there was evidence of increasing metabolic consequences of the diuretic. The study did not define the minimum dose of diuretic, and doses of hydrochlorothiazide lower than 12.5 mg might be as effective. These results suggest that many patients who are being treated with a combination of a beta-blocker and a diuretic are receiving unnecessarily large amounts of the diuretic without benefit to their blood pressure and with adverse metabolic consequences.     

Randomised,double blind,multicentre comparison of hydrochlorothiazide,atenolol, nitrendipine,and enalapril in antihypertensive treatment: results of the HANE study. HANE Trial Research Group.

OBJECTIVE: To compare the effectiveness and tolerability of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in patients with mild to moderate hypertension. DESIGN: Randomised multicentre trial over 48 weeks with double blind comparison of treatments. SETTING: 48 centres in four countries. PATIENTS: 868 patients with essential hypertension (diastolic blood pressure 95-120 mm Hg) INTERVENTIONS: Initial treatment (step 1) consisted of 12.5 mg hydrochlorothiazide (n = 215), 25 mg atenolol (n = 215), 10 mg nitrendipine (n = 218), or 5 mg enalapril (n = 220) once daily. If diastolic blood pressure was not reduced to < 90 mm Hg within four weeks, doses were increased to 25 mg, 50 mg, 20 mg, 10 mg, respectively, once daily (step 2) and after two more weeks to twice daily (step 3). The eight week titration phase was followed by an additional 40 weeks for patients who had reached the target diastolic pressure. MAIN OUTCOME MEASURES: Blood pressure by means of an automatic device with repeated measurements. RESULTS: After eight weeks the response rate for atenolol (63.7%) was significantly higher than for enalapril (50.0%), hydrochlorothiazide (44.7%), or nitrendipine (44.5%). After one year atenolol was still more effective (48.0%) than hydrochlorothiazide (35.4%) and nitrendipine (32.9%), but not significantly better than enalapril (42.7%). The treatment related dropout rate was higher (P < 0.001) in the nitrendipine group (n = 28). CONCLUSIONS: There is no evidence of superiority for antihypertensive effectiveness or tolerability of the "new" classes of antihypertensives (calcium channel blockers and angiotensin converting enzyme inhibitors). As these drugs are now widely used as treatment of first choice, our results further emphasise the need for studies confirming that they also reduce morbidity and mortality, as has been shown for diuretics and beta blockers.     

Attenuation of hypotensive effect of propranolol and thiazide diuretics by indomethacin.

The effects of 100 mg indomethacin daily for three weeks on blood pressure and urinary excretion of prostaglandin F2 alpha were studied in a double-blind, placebo-controlled comparison of two groups of patients with essential hypertension, eight receiving propranolol and seven thiazide diuretics. Compared with placebo, adding indomethacin to the patients'' established antihypertensive treatment increased blood pressure by 14/5 Hg supine and 16/9 mm Hg erect in the patients receiving propranolol, and by 13/9 mm Hg supine and 16/9 mm Hg erect in the patients receiving thiazide diuretics (all p less than or equal to 0.05). The excretion of the major urinary metabolite of prostaglandin F2 alpha was reduced by 67% in the propranolol-treated patients and by 57% in those receiving a thiazide diuretic. Body weight increased by 0 . 8 kg (propranolol) and 1 . 1 kg (thiazide diuretic) when indomethacin was given, but there were no significant changes in creatinine clearance, urinary sodium excretion, or packed cell volume in either treatment group. These results suggest that products formed by the arachidonic acid cyclo-oxygenase contribute to the regulation of blood pressure during treatment with both propranolol and thiazide diuretics. Inhibition of the cyclo-oxygenase with indomethacin partially antagonises the hypotensive effect of these drugs.     

Hypotensive effectiveness and metabolic effects of indapamide in patients with primary arterial hypertension

Indapamide--a non-thiazide diuretic agent--was given to 28 patients with mild and moderate hypertension in a daily dose of 2.5 mg for 12 weeks. Statistically significant decrease in both systolic and diastolic blood pressure and complete normalization of the arterial blood pressure were achieved in 82% of the treated patients. Adverse reactions were mild and transient. However, low but statistically significant decrease in blood serum potassium and changes in the carbohydrate metabolism were seen. No significant effect of the-drug on lipid metabolism was found except the low but statistically significant increase in total cholesterol. Indapamide is an efficient and well tolerated hypotensive agent. However, biochemical indices should be checked up during the treatment due to the potential adverse reactions.     

Mild hypertension: a clinical trial conducted in hospital general practice.

To compare findings in a hospital trial of hypotensive drugs with those in a general practice trial several patients with mild hypertension were studied at the same time in hospital and in general practice. They received bendrofluazide and potassium chloride or bendrofluazide, potassium chloride, and reserpine according to a double-blind crossover protocol, and blood biochemical values were studied over eight weeks and six months. When reserpine was withdrawn from nine women they followed a modified protocol comparing bendrofluazide and potassium chloride with potassium chloride alone. The blood pressure values measured by the general practitioners were similar to those measured in hospital. Both the diuretic alone and the diuretic with reserpine produced significant falls in blood pressures. Although plasma renin activity increased on diuretic treatment, continued treatment did not produce a further increase, and levels gradually declined towards normal.     

The potential for interaction of hydrochlorothiazide with garlic in rats

The present study was undertaken to determine the pharmacokinetic and pharmacodynamic interaction of hydrochlorothiazide (HCTZ) with garlic homogenate (GH), in rats. The influence of garlic on pharmacokinetics of HCTZ was studied by HPLC method, while pharmacodynamic interaction was studied using diuretic activity, ECG and BP changes and isoproterenol (ISO) induced myocardial injury. HCTZ was given orally at 10 mg/kg and GH was administered at three different doses of 125, 250 and 500 mg/kg, p.o. The CK-MB, LDH, SOD, catalase and histopathological studies were carried out. The administration of HCTZ in GH pretreated rats found to decrease the QRS duration, RR interval, QT segment, systolic blood pressure, heart rate, serum potassium level, serum LDH and serum CK-MB activities significantly. The diuretic effect of HCTZ was significantly increased in presence of GH; however, kaliuresis was significantly reduced in presence of GH 250 mg/kg. Histopathological studies of heart tissue reveal the protective effect of GH 250 mg/kg in presence or absence of HCTZ during ISO stress to myocardium. The pharmacokinetic studies show that GH increases the bioavailability and half-life, along with decrease in clearance and elimination rate of HCTZ when administered orally. It was concluded that careful addition of garlic in moderate doses might result in beneficial effect during treatment of hypertension in patients with myocardial stress as garlic causes substantial fall in excretion of potassium when compared to HCTZ alone treatment in rats. This could be important in reducing the dose of HCTZ to achieve enhanced therapeutic effect with minimal adverse effect.     

Comparison of thiazides and amiloride in treatment of moderate hypertension.

The biochemical disturbance produced by thiazide diuretics and by amiloride during treatment of moderate hypertension were compared. Two parallel studies were initiated. In one 40 patients with newly diagnosed hypertension were treated with metoprolol and a diuretic, either hydrochlorothiazide or amiloride. In a second study 38 patients receiving longstanding treatment with hypotensives and thiazides either continued the treatment or replaced the thiazide with amiloride. Initial biochemical assessments were compared with those after two years in the study. In previously untreated patients, thiazide produced a significant fall in plasma potassium and hyperuricaemia that did not occur with amiloride (p less than 0.001). Those patients receiving long term treatment for their hypertension who continued to take thiazides had persistent hypokalaemia and hyperuricaemia. Substitution with amiloride corrected the hypokalaemia and serum uric acid returned toward normal ranges, but this change was not statistically significant. Patients receiving long term treatment also had impaired glucose tolerance, this remained unchanged in those receiving thiazide but was corrected in those receiving amiloride. Compared with amiloride thiazides produced undesirable but reversible biochemical changes. As control of hypertension was equally effective with both preparations, we suggest that a combination of amiloride with a beta blocker in treatment of moderate hypertension in preferred.     

Role of nifedipine in treatment of hypertension.

The efficacy of nifedipine in the treatment of hypertension was assessed in 15 patients whose hypertension continued while being treated with atenolol 100 mg and bendrofluazide 5 mg daily. Nifedipine was added in doses of 10, 20, and 30 mg three times daily in a placebo controlled, double blind trial. One patient was withdrawn from the trial because of severe postural hypotension with the highest dose. Erect and supine blood pressure in the remaining 14 patients were significantly reduced by all doses of nifedipine. The drug was well tolerated but plasma potassium fell by 0.3 mmol(mEq)/1 during treatment (p less than 0.05). Nifedipine is thus effective in the treatment of hypertension but should probably be used in combination with a potassium sparing diuretic.     

Antagonism of the effects of furosemide by in domethacin in normal and hypertensive man

Furosemide and the prostaglandin synthetase inhibitor, indomethacin, were administered singly and in combination to four normal subjects and six patients with essential hypertension in order to determine whether the antihypertensive, natriuretic and other effects of furosemide could be altered by inhibition of prostaglandin synthesis. In all subjects indomethacin treatment alone resulted in a significant elevation of blood pressure and a fall in plasma renin without any change in sodium excretion. Furosemide alone resulted in a significant blood pressure fall with a rise in plasma renin and urinary aldosterone with a marked increase in urinary sodium loss. These effects were either obviated or blunted by addition of indomethacin. The results are compatible with the hypothesis that the antihypertensive and natriuretic effects of furosemide might be mediated at least in part by prostaglandin synthesis. In addition, the effects of indomethacin should be considered when using this drug in hypertensive patients and in subjects requiring diuretic therapy.     

Effect of nifedipine treatment on the renin-aldosterone system and secretion of cortisol and growth hormone in patients with essential hypertension]

The effect of treatment of hypertension with nifedipine on plasma renin activity, blood serum level of aldosterone in the course of renin test, and cortisol and growth hormone concentrations after stimulation with insulin hypoglycemia was followed during two weeks of treatment in 40 patients with essential hypertension. No significant differences in the secretion of the hormones studied, as compared to the patients with the normal arterial blood pressure, were found. After nifedipine treatment no significant changes in the secretion of aldosterone, cortisol and growth hormone were observed despite a significant fall in the arterial blood pressure while there was a moderate stimulatory effect on renin secretion. The results obtained indicate that nifedipine has only small effect on the hormonal system of patients with essential hypertension.     

Controlled trial of long term oral potassium supplements in patients with mild hypertension.

A 15 week randomised double blind placebo controlled trial of oral potassium supplements (48 mmol daily) was conducted in 37 patients who had mildly increased blood pressure and a normal dietary intake of sodium. After a two month run in and a one week baseline period the patients were randomly assigned to receive either potassium supplements (n = 18) or placebo (n = 19). By the third week of treatment blood pressure in the actively treated group had decreased significantly compared with that in the placebo group, though the decrease reached its maximum after 15 weeks. Urinary potassium excretion increased significantly in the group who received potassium supplements, but no significant changes were found in plasma sodium and potassium concentrations or in urinary sodium excretion. In a subgroup of 13 patients who underwent a further nine weeks of treatment with oral potassium supplements at half of the previous dose (24 mmol daily) their blood pressure, at the end of this second study period, was still significantly lower compared with their baseline value but not with that of the placebo group. These results show that moderate oral potassium supplements are associated with a long term reduction in blood pressure in patients who have mild hypertension.     

Beta blockade,diuretics, and salt restriction for the management of mild hypertension: a randomised double blind trial.

Ninety four patients with mild hypertension (average supine diastolic blood pressure (phase V) 95-110 mm Hg) were allocated at random to receive restriction of dietary sodium (maximum allowed 70 mmol(mEq)/24 h) or a normal diet. In addition, they received in random order 25 mg chlorthalidone, 200 mg metoprolol (slow release), and a fixed combination of these two drugs. Each drug treatment was given for four weeks and alternated with four weeks of placebo. Forty four patients were allocated to sodium restriction (group 1) and 50 to normal diet (group 2). The mean 24 hour urinary sodium excretion in group 1 was 74 (SD 31) mmol(mEq)/24 h, and in group 2 132 (51) mmol/24 h. Compared with the screening blood pressure the average decrement of the supine blood pressure in group 1 was 16.0/8.6 mm Hg with placebo, 21.7/11.5 mm Hg with the diuretic, 28.5/17.8 mm Hg with the beta blocker, and 28.9/18.4 mm Hg with the combined agent; in group 2 these values were 13.3/6.1, 20.3/9.7, 21.3/12.9, and 29.4/16.8 mm Hg, respectively. There was a sharp decrease of the average potassium concentration during chlorthalidone and combination treatment periods (average value 3.3 mmol(mEq)/1). These results suggest that moderate salt restriction used as sole treatment has a limited though demonstrable blood pressure lowering effect but that when it is used as an adjuvant to beta blocker treatment its value is greatly enhanced.     

Relation between dose of bendrofluazide,antihypertensive effect,and adverse biochemical effects.

OBJECTIVE--To determine the relevant dose of bendrofluazide for treating mild to moderate hypertension. DESIGN--Double blind parallel group trial of patients who were given placebo for six weeks and then randomly allocated to various doses of bendrofluazide (1.25, 2.5, 5, or 10 mg daily) or placebo for 12 weeks. SETTING--General practices in Zealand, Denmark. PATIENTS--257 Patients with newly diagnosed or previously treated hypertension, aged 25-70, who had a mean diastolic blood pressure of 100-120 mm Hg after receiving placebo for six weeks. MAIN OUTCOME MEASURES--Reduction in diastolic blood pressure and changes in biochemical variables (potassium, urate, glucose, fructosamine, total cholesterol, apolipoprotein A I, apolipoprotein B, and triglyceride concentrations). RESULTS--All doses of bendrofluazide significantly reduced diastolic blood pressure to the same degree (10-11 mm Hg). Clear relations between dose and effect were shown for potassium, urate, glucose, total cholesterol, and apolipoprotein B concentrations. The 1.25 mg dose increased only urate concentrations, whereas the 10 mg dose affected all the above biochemical variables. CONCLUSION--The relevant range of doses of bendrofluazide to treat mild to moderate hypertension is 1.25-2.5 mg a day. Higher doses caused more pronounced adverse biochemical effects including adverse lipid effects. Previous trials with bendrofluazide have used too high doses.     

Moderate sodium restriction with angiotensin converting enzyme inhibitor in essential hypertension: a double blind study.

Fifteen unselected patients who had essential hypertension and whose average supine blood pressure when they were not receiving any treatment and their usual sodium intake was 162/107 mm Hg were treated with captopril 50 mg twice daily. After one month''s treatment their supine blood pressure had decreased to 149/94 mm Hg. They were then instructed to reduce their sodium intake to about 80 mmol(mEq)/day. After two weeks of moderate sodium restriction they were entered into a double blind randomised crossover study comparing the effect of 10 Slow Sodium tablets (100 mmol sodium chloride) with matching placebo tablets while continuing to take captopril and restrict sodium in their diet. After one month of taking placebo their mean supine blood pressure was 137/88 mm Hg with a urinary sodium excretion of 83 mmol/24 h, while after one month of taking Slow Sodium tablets their mean supine blood pressure was 150/97 mm Hg (p less than 0.001) with a sodium excretion of 183 mmol/24 h. The mean supine blood pressure during moderate sodium restriction therefore decreased by 9% and correlated significantly with the reduction in urinary sodium excretion. These results suggest that the combination of treatment with a moderate but practical reduction in sodium intake and an angiotensin converting enzyme inhibitor is effective in decreasing the blood pressure in patients with essential hypertension. This combined approach overcomes some of the objections that have been made to salt restriction alone and to converting enzyme inhibitors alone.     

Long term reduction in sodium balance: possible additional mechanism whereby nifedipine lowers blood pressure.

OBJECTIVE--To assess the changes in sodium excretion and sodium balance after withdrawal of long term nifedipine. DESIGN--Single blind, placebo controlled study in patients receiving fixed sodium and potassium intakes. SETTING--Blood pressure unit of a teaching hospital in south London. PATIENTS--Eight patients with mild to moderate uncomplicated essential hypertension who had been taking nifedipine 20 mg twice daily for at least six weeks. INTERVENTIONS--Withdrawal of nifedipine and replacement with matching placebo for one week. MAIN OUTCOME MEASURES--Urinary sodium excretion and cumulative sodium balance, body weight, plasma atrial natriuretic peptide concentrations, plasma renin activity and aldosterone concentrations, and blood pressure. RESULTS--During nifedipine withdrawal there was a significant reduction in urinary sodium excretion (day 1: -62.7 mmol/24 h; 95% confidence interval -90.3 to -35.0) and each patient retained a mean of 146 (SEM 26) mmol sodium over the week of replacement with placebo. Body weight and plasma atrial natriuretic peptide concentrations increased during the placebo period and seemed to be associated with the amount of sodium retained. Systolic blood pressure rose from 157 (9) to 165 (9) mmHg (95% confidence interval of difference -7.1 to 22.1) when nifedipine was replaced with matching placebo, and the rise seemed to be related to the amount of sodium that was retained. CONCLUSIONS--Nifedipine causes a long term reduction in sodium balance in patients with essential hypertension. This long term effect may contribute to the mechanism whereby nifedipine lowers blood pressure.     

Clonidine reduces elevated cerebrospinal fluid catecholamine levels in patients with essential hypertension

Cerebrospinal fluid (CSF) catecholamines were measured in normotensive patients and in patients with mild to moderate essential hypertension. CSF-norepinephrine (NE) concentrations were 50% lower in the normotensive individuals (127 ± 28 vs. 240 ± 23 pg/m1) (P<0.01). In hypertensive patients, CSF-NE was inversely related to age (r =-0.68; P<0.01) and directly related to plasma NE (r = 0.61; P<0.05). Clonidine (450 mcg/day for 2 weeks) significantly reduced CSF-NE (?40%) in hypertensive patients. In addition, it decreased blood pressure, plasma and urinary NE. Urinary VMA was not affected by clonidine. No correlation was observed between clonidine effects on BP and on plasma or CSF catecholamines. This study indicates that patients with essential hypertension have elevated levels of CSF-NE which are reduced after treatment with clonidine. The elevation of CSF-NE suggests that central (spinal?) noradrenergic activity may be increased in patients with mild to moderate essential hypertension, and that can be reduced by treatment with clonidine.