Comparison of atenolol with propranolol in the treatment of angina pectoris with special reference to once daily administration of atenolol.

Fourteen patients with angina pectoris completed a double blind trial of atenolol 25 mg, 50 mg, and 100 mg twice daily and propranolol 80 mg thrice daily. In comparison with placebo, all active treatments significantly reduced anginal attacks, consumption of glyceryl trinitrate, resting and exercise heart rate, resting and exercise systolic blood pressure, and significantly prolonged exercise time. There was no significant difference between the effects of propranolol and atenolol. Nine patients completed a further trial comparing atenolol given once or twice daily. Both regimens were effective and there was no significant difference between the reductions in anginal attacks, glyceryl trinitrate consumption, systolic blood pressure, or heart rate. Twenty-four-hour ambulatory electrocardiograms showed that atenolol consistently reduced heart rate throughout the 24-hour period whether given once or twice daily. Atenolol is a potent antianginal agent which, in most patients, is likely to be effective once daily.     

Atenolol or propranolol in hypertensive patients poorly controlled on captopril and frusemide

Eighteen patients whose clinic blood pressure (BP) remained over 95 mmHg despite treatment with captopril 50 mg twice daily plus frusemide 40 mg twice daily were randomised in a crossover study to four weeks' treatment with once daily atenolol 100 mg, slow release propranolol 160 mg or placebo. The reduction in BP on atenolol was superior to that on both propranolol and placebo. The mean supine BP 24 hours post dosing were 177/110 mmHg (placebo), 173/109 mmHg (propranolol) and 164/100 mmHg (atenolol). The corresponding mean heart rates were 77 bpm (placebo), 63 bpm (propranolol) and 62 bpm (propranolol) and 62 bpm (atenolol). The difference in hypotensive efficacy between atenolol and propranolol is not readily explained but our study shows that atenolol has a clinically useful supplementary effect on BP. Refractory hypertension remains an important clinical problem and further studies are required to establish the optimum combination of drugs that should be used with captopril in order to achieve 'target' BP in patients with moderate to severe hypertension.     

Comparison of diltiazem and atenolol in young, physically active men with essential hypertension

The antihypertensive efficacy and effect on maximal exercise performance of diltiazem was evaluated and compared with atenolol in patients specifically selected on the basis of their being young and physically active. Diltiazem (sustained-release preparation, 90 mg twice daily) was administered to 14 patients (aged 33 +/- 2 years) and atenolol (50 mg once daily) to 13 patients (aged 30 +/- 2 years) with essential hypertension in a 16-week randomized, double-blind, parallel study. The 2 drugs had comparable antihypertensive effects at rest, with mean decreases of 18 and 17 mm Hg (p less than 0.001) for supine and standing diastolic blood pressure (BP), respectively, during diltiazem treatment, and mean decreases of 21 and 18 mm Hg (p less than 0.001) during atenolol treatment. During maximal graded exercise testing, systolic BP, diastolic BP, heart rate and heart rate-BP product were significantly reduced by both drugs. However, the reductions in systolic BP, heart rate and heart rate-BP product during exercise were considerably greater (p less than 0.001) with atenolol than with diltiazem. Maximal exercise performance was essentially unchanged with diltiazem and slightly (3%, p less than 0.05) reduced with atenolol. Thus, diltiazem is effective and well-tolerated single therapy for young patients with mild to moderate essential hypertension who lead a physically active life style and compares favorably with atenolol.     

Comparative pharmacoclinical study of 2 beta-blockers: atenolol and betaxolol in slight-to-moderate arterial hypertension

Sixteen patients with mild to moderate hypertension were randomized to receive either atenolol 100 mg a day (group A: 2 females, 6 males, mean age 42.3 years) or betaxolol 20 mg a day (group B: 8 males, mean age 49.3 years), both drugs given once daily for one month with a wash out on the 5th day. Pretreatment blood pressure was significantly higher in group B than in group A: this disparity, linked with randomization, hampered the comparison of the antihypertensive efficacy of both drugs but not the comparison of their pharmacodynamics. The maximal effect on resting supine blood pressure occurred later with betaxolol (4th day) than with atenolol (1st day), while the effect on peak exercise-blood pressure and heart rate was rapidly maximal (1st day) for both beta-blockers. The duration of the antihypertensive action at rest seemed to be nearly similar, while the effects of betaxolol on exercising heart rate and blood pressure were more prolonged than those of atenolol: on the wash out day, plasma atenolol and betaxolol levels fell in a same way but the increase in peak systolic blood pressure was more marked in group A than in group B, so that the positive correlation we found between the plasma drug levels and the percentage of peak systolic blood pressure reduction, was much closer with atenolol (p less than 0.001) than with betaxolol (p less than 0.05).     

Double-blind trial comparing labetalol with atenolol in the treatment of systemic hypertension with angina pectoris

Some theoretical arguments suggest that added vasodilation could be beneficial in the management of patients with systemic hypertension and angina pectoris. Ten patients were studied in a double-blind crossover trial in which the severity of hypertension and angina pectoris was monitored. The initial run-in period of 2 to 6 weeks consisted of therapy with fixed-dose atenolol, 100 mg once daily, a thiazide diuretic drug, and any other agents required to control the hypertension. Patients were then randomized for 4 weeks to active atenolol plus 2 tablets of labetalol placebo, or active labetalol (200 mg twice daily) plus atenolol placebo, then crossed over and then changed back to active atenolol without labetalol placebo; the observers were unblinded in the last period. Labetalol and atenolol were equivalent in control of blood pressure at rest, exercise tolerance and use of nitroglycerin; however, heart rates at rest and during exercise were higher with labetalol (p less than 0.01), whereas the heart rate-blood pressure product at the end of the exercise test was unchanged with labetalol. The higher heart rates for the same antianginal efficacy may give an advantage to labetalol treatment in some patients. Conversely, atenolol is cardioselective, hydrophilic, and can be given as a single daily dose. Thus, each agent has some advantages in the therapy of patients with hypertension and effort angina.     

Ambulatory blood pressure profiles in essential hypertensives after treatment with a new once daily nifedipine formulation

The antihypertensive efficacy of a new controlled-release preparation of nifedipine developed for once daily administration was investigated in comparison with a standard therapy with sustained-release nifedipine given twice daily in a randomised, open crossover trial. Twenty-two patients with mild to moderate essential hypertension were enrolled. Ambulatory blood pressure monitoring (ABPM) was performed after a wash-out period and after a 3 weeks treatment with 40 mg controlled-release nifedipine once daily and 20 mg sustained-release nifedipine twice daily, respectively. ABPM data were evaluated by conventional linear analysis and by rhythm analysis. Both once daily and twice daily administration of nifedipine significantly reduced systolic blood pressure during the daytime and during the night when compared with baseline. The 24-h diastolic blood pressure was significantly decreased by both treatments, but only the once daily regimen significantly lowered both diastolic daytime and night-time means. Comparing systolic and diastolic blood pressures after both treatments, however, no significant differences were obtained. Both nifedipine treatments did neither greatly modify the circadian blood pressure pattern nor reflexly increase heart rate. In conclusion, once daily application of the controlled-release formulation of nifedipine resulted in a consistent and significant blood pressure reduction. Once daily and twice daily medications of nifedipine were about equally effective in lowering the elevated blood pressures.     

Sustained-release diltiazem compared with atenolol monotherapy for mild to moderate systemic hypertension

The daily administration of 240 to 360 mg of diltiazem lowered blood pressure in a dose-related pattern similar to that seen in patients taking a daily dosage of 50 to 100 mg of atenolol. Sustained-release diltiazem was administered twice daily and atenolol once. Goal blood pressure was defined as less than 90 mm Hg or a reduction of greater than or equal to 10 mm Hg for patients with baseline pressures of 95 to 99 mm Hg in the supine position and was achieved in 60% of diltiazem-treated and 63% of atenolol-treated patients. The mean diltiazem dosage at the end of the study was 329 mg daily; for atenolol it was 80 mg daily. Adverse reactions considered possibly or probably drug related were reported by 26% of diltiazem patients and 38% of atenolol patients. Although both drugs were associated with a slower heart rate, atenolol patients showed a significantly greater negative chronotropic effect. Diltiazem, in a sustained-release form taken twice daily, is as effective as atenolol as a sole antihypertensive agent. It has a favorable side-effect profile and may be a useful alternative antihypertensive medication compared with existing beta-blocker therapy with atenolol.     

The chronic effect of rilmenidine on heart rate variability in patients with mild hypertension

The purpose of this study was to evaluate the chronic effect of rilmenidine on time domain indexes of heart rate variability in patients with mild hypertension. Twenty patients (12 males, eight females; mean age, 47 yr; age range, 38-55 yr), with untreated and newly diagnosed mild hypertension were studied. There was no evidence of diseases other than hypertension. All patients received 1 mg of rilmenidine once daily. If the diastolic blood pressure was still greater than 90 mm Hg after 4 weeks of active treatment, the dose was increased to 2 mg once daily. Twenty-four hour ambulatory electrocardiograms were recorded before, and 4 and 12 weeks after the start of therapy. Time domain parameters of heart rate variability were calculated. Rilmenidine therapy determined a marked decrease in blood pressure. At 4 weeks, rilmenidine induced a significant reduction in systolic and diastolic blood pressure and a further reduction was observed after 12 weeks. At 4 and 12 weeks, time domain parameters of heart rate variability and heart rate were not significantly different in the data obtained before therapy. In conclusion, this study demonstrated that the administration of rilmenidine to patients with mild essential hypertension induced significant reductions in blood pressure, without any significant changes in time domain parameters of heart rate variability.     

Nebivolol: Comparison of the Effects of dl-Nebivolol, d-Nebivolol, l-Nebivolol, Atenolol, and Placebo on Exercise-Induced Increases in Heart Rate and Systolic Blood Pressure

The effects of racemic nebivolol, 2.5, 5.0, and 10.0 mg; d-nebivolol, 2.5 mg; l-nebivolol, 2.5 mg; atenolol, 50 mg; and placebo, each given once daily for 7 days, on exercise-induced increases in heart rate and systolic blood pressure were compared in a seven-way double-blind randomized crossover trial in 14 healthy male volunteers. Observations on these variables were made 3 and 24 hours after dosing on the first and last days of therapy. Similar effects on both exercise-induced tachycardia and increases in systolic blood pressure were seen with nebivolol 5.0 mg and with d-nebivolol 2.5 mg; l-nebivolol 2.5 mg was no different from placebo. These data show that the beta-blocking effects of nebivolol reside in the d-isomer. A dose-related response was evident with racemic nebivolol in inhibiting exercise-induced tachycardia over the range of doses studied. Whereas the effects of atenolol on both exercise-induced tachycardia and increases in systolic blood pressure were fully evident on the first day of treatment, those of nebivolol, especially with regard to heart rate, and, to a lesser degree, systolic pressure, were greater on the final than on the first day. Nebivolol had a clearly superior trough-to-peak efficacy ratio than atenolol.     

Comparative trial of nifedipine retard and atenolol in the treatment of elderly patients with mild to moderate hypertension

Forty-one elderly patients with mild to moderate hypertension (resting diastolic blood pressure 100-130 mmHg after an eight week placebo run-in phase) were randomised to a double-blind parallel group comparison of nifedipine retard 10 mg twice daily or atenolol 50 mg once daily. If the resting diastolic pressure exceeded 95 mmHg after four weeks of treatment the dose(s) were doubled for a further four weeks. Initial sitting blood pressures were 187 +/- 21/105 +/- 5 mmHg in the nifedipine group and 181 +/- 19/106 +/- 6 in the atenolol group. At four weeks, eight patients given nifedipine and nine given atenolol had their doses doubled. At eight weeks sitting blood pressures were 159 +/- 19/85 +/- 7 and 162 +/- 21/87 +/- 8 respectively, with 18/20 patients given nifedipine and 16/21 given atenolol having a sitting diastolic pressure equal to or less than 95 mmHg. One patient given nifedipine was withdrawn because of unacceptable ankle oedema and one given atenolol withdrawn because of worsening angina. Both drugs were equally acceptable to the patients and neither caused a change in their sense of well-being.     

Effects of atenolol and diltiazem-SR on exercise and pressure load in hypertensive patients

The effects of monotherapy with atenolol or diltiazem-SR on blood pressure, 24-h blood pressure (BP) load, and exercise capacity were tested in patients with mild to moderate (stages I and II) essential hypertension. After 3-week single blind placebo therapy, patients with sitting diastolic blood pressure (SDBP) of 94-114 mmHg were randomized to atenolol 50 mg/day (62 patients) or diltiazem-SR 90 mg b.i.d. (60 patients) in a double-blind parallel study. Depending on SDBP response, the dose was increased to 100 mg/day for atenolol and 180 mg b.i.d. for diltiazem-SR. Twenty-four-hour ambulatory blood pressure measurements and exercise tolerance lest by the Bruce protocol were done at the end of placebo and active treatment. Compared with placebo, both atenolol and diltiazem-SR significantly decreased heart rate (HR), sitting systolic blood pressure (SSBP), SDBP, ambulatory BP, BP load for waking and sleeping hours, area under the BP curve, rate-pressure product (p < 0.001), and exercise time (NS). Atenolol exerted a greater effect on ambulatory BP, HR, rate-pressure product, waking diastolic BP load, and area under the 24-h BP curve. The drugs were well tolerated and caused no serious side effects necessitating discontinuation of treatment. These findings indicate that (1) monotherapy for hypertension with atenolol or diltiazem SR is effective and well tolerated, (2) it decreases the 24-h BP load, (3) it does not interfere with exercise capacity.     

A Comparison of 100 mg Atenolol and 100 mg Metoprolol Once a Day at Rest and during Exercise in Hypertensives

Abstract The effects of once daily dosage of the two cardioselective β-adrenoceptor blocking agents, atenolol and metoprolol, were studied in 26 patients with primary hypertension. The study was a randomized double-blind cross-over trial with placebo run-in and wash-out. Assessment of effect was performed about 1 and 25 hours after dosing. At rest, both atenolol and metoprolol lowered the blood pressure (BP) and heart rate (HR) compared to placebo. Atenolol induced a more effective BP reduction than metoprolol, especially 25 hours after drug intake. During exercise 1 hour after dosing both drugs reduced BP and HR to a similar extent, whereas 25 hours after dosing atenolol gave a more efficient BP and HR reduction than metoprolol. Our data show that both 100 mg atenolol and 100 mg metoprolol are effective antihypertensive β-blockers at rest and during exercise, 1 hour after intake. Metoprolol was less effective than atenolol 25 hours after dosing probably due to its shorter plasma half-life, thus implying a twice daily regimen for metoprolol in standard preparation.     

Comparison of nicorandil and atenolol in stable angina pectoris

The efficacy of nicorandil was compared with atenolol in 37 patients with chronic stable angina using a randomized, placebo-controlled, parallel study design. After a single-blind placebo phase, patients were randomized to receive nicorandil or atenolol using a double-dummy technique. Patients took nicorandil 10 mg twice daily or atenolol 50 mg once daily for the first 3 weeks, and if no adverse effects were encountered they took nicorandil 20 mg twice daily or atenolol 100 mg once daily, for the final 3-week phase. Treadmill exercise tests were performed at the end of each treatment phase immediately before and 2 hours after the morning dose of medication. Groups were demographically similar. Placebo exercise times were 7.06 (0.60) minutes (mean +/- standard error of the mean) in the nicorandil group and 6.81 (0.47) minutes in the atenolol group. After 6 weeks, improvements in exercise time were before dosing: +1.47 (0.40) minutes with nicorandil (p less than 0.005) and +1.33 (0.29) minutes with atenolol (p less than 0.001). Improvements after therapy was administered were +2.45 (0.41) minutes with nicorandil (p less than 0.001) and +2.37 (0.43) minutes with atenolol (p less than 0.0001). Whereas, the predose peak exercise double product (heart rate X systolic blood pressure mm Hg/100) was reduced with atenolol (-43.6 units; p less than 0.001), an increase (+7.56 units; difference not significant) was noted with nicorandil. One patient taking atenolol and 5 taking nicorandil developed persistent headaches. One subject with severe 3-vessel coronary artery disease had fatal myocardial infarction within 3 days of starting nicorandil, 10 mg twice daily.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amlodipine versus atenolol in essential hypertension

The efficacy and safety of amlodipine (2.5–10 mg) once daily was compared with atenolol (50–100 mg) once daily in patients with mild-to-moderate essential hypertension in a randomized, doubleblind, parallel, placebo-controlled study. A total of 125 patients were randomly allocated at the end of a 4-week run-in placebo period to 8 weeks of double-blind treatment with amlodipine (n = 41), atenolol (n = 43), or placebo (n = 41). The placebo group had small mean changes in supine and standing blood pressure compared with baseline. The mean blood pressure changes from baseline 24 hours postdose in the amlodipine group (mean daily dose 8.8 mg) were −12.8/−10.1 mm Hg for supine blood pressure and −11.5/−9.8 mm Hg for standing blood pressure (p < 0.001 compared with placebo), and for the atenolol group (mean daily dose 83.7 mg) the changes were −11.3/−11.7 mm Hg for supine blood pressure and −13.3/−12.3 mm Hg for standing blood pressure (p < 0.001 compared with placebo). There were no statistically significant blood pressure differences between active treatments. The responder rates for amlodipine, atenolol, and placebo were 61.1, 64.9, and 11.1%, respectively. The blood pressure values taken over the 24-hour period at final visit revealed that amlodipine and atenolol maintained the supine blood pressure ≤ 140/90 mm Hg throughout the period of observation; the corresponding time-effect curve for the placebo group was clearly in the hypertensive range. Heart rate was significantly lowered by atenolol only. Both amlodipine and atenolol were well tolerated. Only 1 patient was withdrawn due to adverse effects (development of peripheral edema, arthralgia and fatigue) related to amlodipine. This study demonstrates that once-daily therapy with amlodipine or atenolol was well tolerated in patients with mild-to-moderate essential hypertension and provided control of blood pressure throughout the 24-hour dosing interval.     

Amiloride compared with nitrendipine in treatment of essential hypertension

The antihypertensive effect of amiloride was compared to that of the calcium antagonist nitrendipine in 12 patients (8 males), aged 34-62 years, with essential hypertension WHO grade I-II (mean supine blood pressure 158/103, standing 155/106 mmHg) in a double-blind placebo-controlled cross-over study design. Amiloride was given 5 mg once daily for one month followed by 20 mg twice daily for another month. Amiloride 5 mg once daily significantly reduced supine and standing DBP but not SBP (supine 151/94, standing 149/97 mmHg), whereas 10 mg once daily decreased SBP as well as DBP (supine 145/98, standing 145/101 mmHg). Nitrendipine 20 mg once daily significantly reduced supine and standing SBP and standing DBP (supine 150/97, standing 148/98 mmHg), but on 20 mg twice daily only supine SBP was significantly reduced (supine 150/99, standing 151/106 mmHg). Heart rate was transiently increased by nitrendipine 20 mg once daily and unchanged following amiloride. Plasma noradrenaline was unaltered following amiloride 10 mg once daily as well as nitrendipine 20 mg twice daily, whereas plasma renin activity and aldosterone were elevated following amiloride. Serum electrolytes, blood glucose, plasma lipids and body weight were not altered by any of the drugs. Amiloride 5-10 mg daily has a mild to moderate BP lowering effect in patients with essential hypertension. The BP reduction following nitrendipine 20 mg once daily was comparable to that of amiloride 5 mg daily. Nitrendipine 20 mg twice daily gave no additional BP decrease.     

Effects of the Calcium Antagonist Felodipine on the Sympathetic and Renin-Angiotensin-Aldosterone Systems in Essential Hypertension

ABSTRACT Studies were performed in 10 male patients with untreated essential hypertension, WHO grade I-II, aged 25–62 years, to explore the acute (single dose) and long-term (8 weeks) effects of felodipine on sympathetic activity—evaluated by plasma and urinary catecholamines—as related to blood pressure, heart rate and the activity in the renin-angiotensin-aldosterone system. The patients were hospitalized for 8 (acute) and 6 (long-term) days and were maintained on a standardized daily intake of sodium (150 mmol), potassium (75 mmol) and water (2500 ml). Acute felodipine administration (10 mg) significantly reduced blood pressure and increased heart rate. Plasma and urinary noradrenaline, plasma renin activity and angiotensin II increased, whereas plasma and urinary adrenaline, dopamine, aldosterone and plasma vasopressin were unaltered. Long-term felodipine treatment, 10 mg twice daily, reduced blood pressure to a similar extent as acute felodipine administration, but heart rate was not significantly changed. Plasma noradrenaline 3 and 12 hours after the last dose and urinary noradrenaline were increased, whereas plasma and urinary adrenaline and dopamine were unchanged. Plasma renin activity and angiotensin II were increased 3 hours, but unchanged 12 hours after the last dose. Plasma aldosterone was unchanged but urinary aldosterone increased. Plasma vasopressin was unchanged. The changes in plasma noradrenaline as related to blood pressure, heart rate, plasma renin activity and angiotensin II during long-term felodipine treatment may reflect decreased cardiac and renal β-adrenoceptor-mediated responses. Increased renal clearance of aldosterone could partly explain the unaltered plasma aldosterone level in spite of increased plasma angiotensin II following long-term felodipine treatment.     

Different hemodynamic (24-h ambulatory blood pressure monitoring) and renin-inhibiting effect of a 1-week treatment with enalapril and lisinopril.

Ambulatory blood pressure and heart rate monitoring were used for comparing the antihypertensive effect of a 1-week treatment with enalapril and lisinopril 10 mg once daily (double-blind crossover placebo-controlled study). Twelve outpatients with mild to moderate hypertension were treated. Both drugs had a significant and identical hypotensive effect. Neither drug affected the diurnal rhythm of blood pressure or heart rate. Therefore the two drugs are equipotent antihypertensive agents. Both drugs inhibited ACE activity to a highly significant extent, but in this regard lisinopril was more effective than enalapril. However, lisinopril's greater ACE inhibition was not accompanied by a greater hypotensive effect. The clinical value of this difference is not yet established.     

Diltiazem and atenolol in essential hypertension: additivity of effects on blood pressure and cardiac conduction with combination therapy

In 15 patients with mild to moderate essential hypertension, the effects of diltiazem (120 mg twice daily) were compared with those of atenolol (50 mg once daily), the two drugs in combination, and placebo in a randomized double-blind cross-over study with treatment phases of 4 weeks duration. Blood pressure was reduced in the active treatment phases (supine blood pressure: diltiazem, 172/92 mmHg; atenolol, 172/92 mmHg; diltiazem plus atenolol, 164/88 mmHg; pooled estimate of s.e.m. by analysis of variance = 3/1) compared with placebo (180/101 mmHg). Factorial analysis confirmed fully additive antihypertensive effects of the drugs in combination. The time interval from the beginning of the P wave to the beginning of the QRS complex (P-R interval) was longer during combination therapy (0.184s) compared with either diltiazem (0.175s) or atenolol (0.174s) alone, or placebo (0.164s); s.e.m. by analysis of variance = 0.003. No clinically significant conduction disturbances occurred. Plasma atrial natriuretic peptide was elevated by atenolol but not diltiazem. Thus, in subjects with uncomplicated essential hypertension, diltiazem and atenolol had equal antihypertensive efficacy when used alone, and fully additive effects in combination, on both blood pressure and cardiac conduction.     

Beta-blocker versus diuretic for control of the blood pressure response to stress in hypertensive patients

To compare the antihypertensive effects of beta-blockers and diuretics on the blood pressure increase to stress, a randomized single-blind crossover study was performed in 27 patients with mild or moderate hypertension. At the initial examination and after two subsequent periods of therapy with 100 mg atenolol or with a combination of 50 mg hydrochlorothiazide and 5 mg amiloride hydrochloride, once a day, blood pressure and heart rate were measured at rest, during mental arithmetic, sustained handgrip and cycloergometric test. Both treatment significantly decreased supine and standing systolic and diastolic pressure at rest, during and immediately after mental stress and isometric exercise, with the reduction of diastolic pressure significantly greater after atenolol. During dynamic exercise, systolic and diastolic pressures were significantly decreased by diuretics at the lowest work-load only, whereas beta-blocker caused significant and greater blood pressure reductions throughout the exercise. The combination of two classes of drug normalized resting blood pressure in 8 of 9 subjects in which the monotherapy had failed to obtain values less than 140/90 mmHg and gave a better control of systolic and diastolic pressures throughout all the stress tests. It is concluded that atenolol is more effective than diuretics during stress, suggesting that beta-blocking drugs are the first choice treatment for mild to moderate hypertension and that when the antihypertensive effect of a single agent is insufficient, a combination of beta-blockers and diuretics is also effective during stress.     

Production and Reversal of Doca-Salt Hypertension in Baboons

We describe for the first time a non-human primate model of mineralocorticoid-salt hypertension. Baboons instrumented for chronic, direct measurement of arterial pressure, underwent sodium chloride loading (8.6 or 17.1 mEq/kg/day) by different routes for several weeks and deoxycorticosterone acetate (DOCA) 5 mg/2 days i.m., in addition to sodium chloride, for periods lasting up to several months. Salt loading alone at 8.6 mEq/kg/day had no chronic effect on mean arterial pressure (MAP). Salt loading at both doses in combination with DOCA produced increases in MAP within a few days which became progressively larger over weeks to months. DOCA-salt hypertension was associated with hyporeninemia and mild hypokalemia, without consistent changes in heart rate or plasma catecholamines. A biofeedback procedure applied to three animals failed to reduce tonic blood pressure. in two of these animals, administration of clonidine or atenolol also had no antihypertensive effect, whereas a diuretic combination (hydrochlorothiazide and triamterene) rapidly abolished the hypertension. The absence of amelioration of the hypertension by a central sympatholytic agent or a β-adrenoceptor blocker, coupled with the absence of increased plasma catecholamines, suggests that increased sympathetic activity may not contribute to the hypertension in contrast with findings in lower animals but consistent with clinical reports.