Long-term Treatment Of Hypertension Research Articles

Tolérance du perindopril dans l'hypertension artérielle. Résultats d'une étude multicentrique européenne

Long term acceptability of perindopril was evaluated in 856 hypertensive patients (52.9 ± 0.4 years) including 21.3 patients > 60 years. Mean duration of treatment was 21 months (3 days-48 months). In younger (≤ 60 years ) and older patients, adverse events were reported at the same incidence with the higher incidence for cough 6.8 and 7.5 % respectively. Increase in serum creatinine (141–195 μmol/l) was observed in 27 patients including 9 > 60 years. These results show the good acceptability of perindopril in the long term treatment of hypertension.

Effects of short- and long-term administration of nifedipine on serum lipoprotein metabolism in patients with mild hypertension

The effects of short- and long-term administration of nifedipine on serum lipids, lipoproteins, and apolipoproteins (apo) were studied. Administration of nifedipine capsule for 4 months significantly decreased triglycerides and increased the HDL2 cholesterol and the HDL2/HDL3 cholesterol ratio. No significant changes in serum lipids and lipoproteins were observed during short-term therapy with slow-release nifedipine tablets. Following administration of tablets for 24 months, the LDL/HDL cholesterol ratio, apo B, and apo B/apo A-I ratio increased at 12 months, but reverted to baseline values at 24 months. Apo E levels were decreased significantly at 24 months. No significant changes were noted in total cholesterol, triglyceride, HDL cholesterol, HDL2,3 cholesterol, apo A-I, apo A-II, apo C-II, or apo C-III levels during long-term therapy with slow-release nifedipine tablets. These results indicate that nifedipine has a neutral or even favorable effect on lipoprotein metabolism. However, a prospective well-controlled study would be required to finally establish this effect. This finding strengthens the indications for using nifedipine as a first-line drug in the long-term treatment of hypertension.

Enalapril in the Long-Term Treatment of Elderly Hypertensives

The long-term antihypertensive effects of enalapril were assessed for a period of up to 1 year in 44 elderly patients with mild-to-moderate essential hypertension. Following a 2-week placebo period, patients who were assigned to enalapril were followed for 6 weeks in a randomized clinical trial. In patients who benefited from enalapril, treatment was continued and subjects were followed for up to 1 year. Supine and standing systolic and diastolic blood pressures were significantly reduced throughout the 1-year period compared with baseline. The dosage of enalapril was increased from 10 to 20 mg daily in 12 patients; 8 required additional antihypertensive agents. Enalapril is effective in the long-term treatment of hypertension; no loss of antihypertensive agents. Enalapril is effective in the long-term treatment of hypertension; no loss of antihypertensive effect occurs.

Long-Term Treatment of Hypertension with Felodipine

Hypertensive patients who had previously taken part in double-blind, controlled studies were treated with open-label felodipine for 1 year: 377 had felodipine added to a beta-blocker and 94 were receiving monotherapy. In the first group, supine blood pressure (BP), measured at the beginning of the double-blind period, was reduced from 172 +/- 23/107 +/- 8 to 140 +/- 20/86 +/- 8 mm Hg at the end of 1 year of therapy. In the monotherapy group, BP was reduced from 170 +/- 22/101 +/- 7 mm Hg measured before treatment to 149 +/- 17/90 +/- 9 mm Hg after 1 year. The most common adverse experiences that led to withdrawal were peripheral edema, headache, flushing, and dizziness. No development of tolerance was noted.

Long-term treatment of hypertension in the elderly with a combination of atenolol and nifedipine

The efficacy and tolerability of a once-daily, fixed combination of 50 mg atenolol and 20 mg nifedipine slow release were evaluated in a 12-month open study of 27 elderly hypertensives who were either newly presenting patients or were those who were inadequately controlled on previous monotherapy or had unacceptable side-effects with their current therapy. After 1-month's therapy with the combination, the mean sitting blood pressure 1 to 4 hours post-dose decreased from 176/103 mmHg to 146/83 mmHg and was maintained at this level for the remainder of the study. Eight patients complained of side-effects on study entry. Sixteen had complaints at some time during the 12 months of fixed combination treatment and 4 were withdrawn because of side-effects. Dizziness occurred in 6 patients on the combination but, as with side-effects overall, tended to resolve with time; its occurrence did not appear to correlate with the on-treatment blood pressure. In this group of elderly hypertension patients, therefore, the combination therapy with atenolol plus nifedipine slow release appeared to exert a greater antihypertensive effect compared with previous therapy, which included atenolol alone, with no evidence of tachyphylaxis and was reasonably well-tolerated over a 12-month period.

Recent trend in the research of hypertension in Japan. Problems on the long-term treatment of hypertension--withdrawal of antihypertensive drugs and regression of cardiac hypertrophy

Recent trend in the research of hypertension in Japan. Problems on the long-term treatment of hypertension--withdrawal of antihypertensive drugs and regression of cardiac hypertrophy

Antihypertensive Effects of Niguldipine-HCl (B 844–39), a New Calcium Antagonist in Dogs

B 844-39 is a new dihydropyridine calcium antagonist with a long-lasting antihypertensive action. Preliminary tests in chronically instrumented normotensive dogs revealed that B 844-39 (0.3 mg/kg p.o.) caused a marked decrease in blood pressure which was accompanied by a counterregulatory increase in heart rate. Both effects outlasted the 6-h observation period. There was no sign of cardiac depression in left ventricular positive dP/dtmax or sonomicrometrically evaluated subendocardial systolic shortening. B 844-39 was also tested in renal hypertensive dogs over a period of 12 days to investigate its potential in the long-term treatment of hypertension. A dosage of 0.3 mg/kg given orally twice a day led to a marked and persistent decrease in blood pressure, which was accompanied by a positive chronotropic effect and increases in plasma renin activity and angiotensin II. This initial counterregulatory response was blunted within several days of chronic treatment. After completion of the 12-day treatment period, the blood pressure reduction persisted for greater than 14 days. B 844-39 induced a marked and persistent reduction in blood pressure in hypertensive dogs, even with prolongation of the dosing interval to 24 h. The hypotensive effect of this drug was more pronounced in hypertensive than in normotensive animals.

Effects of antihypertensive treatment on cerebral perfusion

Antihypertensive treatment reduces the risk of ischemic strokes and cerebral hemorrhage as complications of excessive or longstanding hypertension. However, neurologic dysfunction and brain damage may also accompany short-term, and under certain conditions, even long-term antihypertensive treatment. Therefore, treatment should be instituted restrictively and cautiously. Special regard should be given to the action of antihypertensive drugs on cerebral perfusion in patients with an increased risk for the development of treatment-induced cerebral ischemic complications, such as patients with hypertensive encephalopathy or autonomic dysfunction, and elderly patients with suspected sclerotic stenosis of cerebral or neck arteries. The structural and functional lesions of cerebral vessels observed in acute and chronic hypertension are reviewed, as are the effects of antihypertensive drugs on cerebral blood flow. Calcium channel blockers and angiotensin-converting enzyme inhibitors may have advantages as first-line drugs in the treatment of patients with an elevated risk of cerebral hypoperfusion, because of the selective action of these agents on vasocon-stricted vessels and their differential effects in varying regional vascular beds. The excellent efficacy of these drugs in the short- and long-term treatment of hypertension may lead to changes in the traditional management of hypertensive emergencies as well as in management strategies for other patients at risk for treatment-induced complications.

Antihypertensive and biochemical effects of the dihydropyridine felodipine in the long term treatment of moderate to severe hypertension.

Twenty-seven patients with severe hypertension, in 19 cases accompanied by renal failure, were treated with felodipine, a new dihydropyridine calcium antagonist, 23 patients completed a 24-week, and 19 a 48-week follow-up. At the end of the follow-up, felodipine was given in combination with a β-adrenoceptor blocking drug in most instances (80%), but in 60% of the cases no diuretic was needed. Antihypertensive treatment with felodipine caused a 25% reduction in blood pressure, which was sustained throughout follow-up. The drug was well tolerated and was as effective in patients with renal insufficiency as in patients with normal renal function. Plasma creatinine levels remained stable throughout follow-up. Plasma calcium levels rose during felodipine therapy. This finding could not be related to the change in blood pressure or to the use of thiazide diuretics. The data confirm the potency of felodipine in the long term treatment of hypertension.

Serum lipoprotein levels during long-term treatment of hypertension with indapamide.

The beneficial effect of antihypertensive pharmacotherapy in decreasing morbidity and mortality in hypertensive patients may be counteracted by metabolic and biochemical disturbances, such as hypokalemia, hyperglycemia, hyperuricemia, and hyperlipoproteinemia, that occur with the administration of thiazides and related diuretics. Antiatherogenic high-density lipoprotein cholesterol may be unchanged, whereas the potentially atherogenic low-density lipoprotein cholesterol may be increased by long-term therapy with thiazide diuretics. Indapamide is a methylindoline antihypertensive diuretic with a considerable peripheral vasodilatory effect. At a low dose of 2.5 mg daily, it did not alter total circulating cholesterol, in contrast to chlorthalidone. High-density lipoprotein cholesterol levels increased significantly in 20 hypertensive men after 6 months of therapy with indapamide, resulting in a significant fall of the low-density lipoprotein/high-density lipoprotein ratio, an atherogenic risk factor, regardless of preexisting lipid disorders.

Long Term Treatment of Hypertension in the Elderly

Long Term Treatment of Hypertension in the Elderly

Captopril: Long-Term Treatment of Hypertension in a Preterm Infant and in Older Children

• Five children with high-renin hypertension unresponsive to conventional medications were effectively treated with the angiotensin I—converting enzyme inhibitor, captopril, for six to 26 months. Age groups included children 6 to 13 years old and a 33-week gestation preterm infant with hypertension related to umbilical artery catheterization. Significant adverse reactions were limited to transient renal insufficiency in the preterm infant and increased azotemia in an older child with chronic renal failure. (Am J Dis Child1983;137:263-266)

Calcium antagonists. Clinical use in the treatment of systemic hypertension.

Increased peripheral vascular resistance is the cause of elevated systemic blood pressure in most patients with long standing hypertension. The desired haemodynamic effect in antihypertensive therapy is dilation of the constricted arterioles by a drug that acts directly on the vascular smooth muscle while not affecting the heart or the venous return. Hydralazine, diazoxide and minoxidil act directly on vascular smooth muscle to produce vasodilatation and have been used with variable degrees of success in the long term treatment of hypertension. Their cellular mechanism of dilation is not understood fully, but the ability to chelate certain trace metals required for smooth muscle contraction has been proposed as a possible mechanism of action for these drugs. The calcium antagonists (calcium entry blocking drugs) are a distinct group of compounds that interfere with the normal transmembrane flux of extracellular calcium ions on which vascular tissue depends for contraction or impulse generation. Thus, calcium anti-agonists can reduce the contractile activity of the heart, and promote coronary and systemic vasodilatation. These effects provide the clinical rationale for the use of calcium antagonists in the management of ischaemic heart disease and hypertrophic cardiomyopathy. Since systemic vasodilatation can be expected to reduce elevated arterial blood pressure, interest has focused recently on calcium antagonists in the medical management of systemic hypertension. All the calcium antagonists are able, in low concentrations, to relax the smooth muscle vasculature from coronary, cerebral, mesenteric, and renal arteries. The effects on the myocardium, cardiac impulse tissue, and vascular smooth muscle are different in magnitude, however, depending on the individual agent that is used. Clinical experience in the treatment of hypertension with this class of agents is confined to verapamil, nifedipine, and diltiazem. In this article, the scientific rationale for using calcium antagonists in the treatment of arterial hypertension is explored and the clinical experiences with the different calcium antagonists used in hypertension are reviewed.

Plasma clonidine in relation to blood pressure, catecholamines, and renin activity during long-term treatment of hypertension.

Eight patients with essential hypertension were treated with 50 microgram oral clonidine four times daily for 4 wk followed by 75 to 150 microgram four times daily for another 4 to 16 wk. Before treatment and at the end of each treatment period the patients were hospitalized and their plasma clonidine concentrations (P-CLON) were determined repeatedly during one dosage interval. The relationship of P-CLON to blood pressure, heart rate, plasma norepinephrine (PNE), and plasma renin activity (PRA), as well as to conventional kinetic parameters, was calculated. With the two dosages used the half-life (t 1/2 s) of clonidine absorption were 1.05 and 0.83 hr, the biological t 1/2 s 8.7 and 7.9 hrs, and the total oral clearances 4.7 and 5.0 ml X min-1 X kg-1. The log of P-CLON correlated with the maximum percentage decrease of mean arterial blood pressure (MAP) (r = 0.91, P less than 0.001) in five patients, whereas in three patients there was no further decrease of MAP after increase of plasma clonidine level. The logarithm of P-CLON correlated with percentage reduction of PNE (r = 0.67, P less than 0.01). In six patients in whom clonidine induced a reduction of PRA, there was a relationship between log P-CLON and percentage PRA reduction (r = 0.91, P less than 0.001) and also between the percentage PRA and PNE reduction (r = 0.74, P less than 0.01).

Coronary Risk in Patients with Endstage Renal Disease

Uremic patients treated with hemodialysis develop accelerated atherosclerosis. The factors responsible for this are hypertension, abnormal lipid and carbohydrate metabolism, cigarette smoking, a sedentary lifestyle and perhaps the dialysis process itself. Hypertension and hyperlipidemia are common in dialysis patients and may be major coronary risk factors in this population. Most hypertensive dialysis patients respond to ultrafiltration and control of volume expansion with a normalization in blood pressure, but 20 to 30% require antihypertensive therapy. The treatment of this hypertension requires agents that either reduce peripheral vascular resistance, plasma renin, or both The hyperlipidemia in dialysis patients is characterized by hypertriglyceridemia, reduced high density lipoprotein cholesterol (HDL-C) levels and low apoprotein Cll levels. The treatment of these lipid abnormalities is difficult because they are numerous and the use of certain drugs is restricted due to impaired renal function The prevention of coronary heart disease involves the identification and treatment of existing coronary risk factors and protection from the development of new ones. The long-term treatment of hypertension appears to reduce cerebrovascular, but not cardiovascular mortality in nonuremic patients. This appears to be due to the reduction in blood pressure caused by the antihypertensive therapy used in these studies. However, some of these drugs have a deleterious effect on lipid metabolism. Agents that alter lipid metabolism in such a fashion. especially in dialysis patients with hyperlipidemia, would increase the magnitude of these abnormalities. Sustained hyperlipidemia. in combination with hypertension, might promote atherogenesis even more rapidly In nonuremic patients, propranolol raises plasma triglyceride levels and reduces HDL-C concentrations, while prazosin has a neutral effect. In dialysis patients, however. HDL-C levels were higher on prazosin (51 ± 7 mg/dl. ━●━ ± SE. n = 6) than propranolol (38 ± 4. n = 6). When antihypertensive therapy was used in dialysis patients already on nandrolone decanoate (an androgen used to increase red blood cell production). HDL-C levels were higher on prazosin (41 ±4 mg/dl. n = 14) than propranolol (32 ± 2, n = 13. p

Residential mobility and long-term treatment of hypertension.

Maintenance of long-term care of populations with high mobility patterns poses problems for programs designed to prevent and treat cardiovascular and other chronic diseases. The Hypertension Detection and Follow-up Program (HDFP)--a community-based screening and treatment program implemented in 1973--provided an opportunity to examine residential mobility among adults under long-term treatment in 13 communities. Whereas 11% of hypertensives included in the HDFP changed residence in the first two years of the study, only 4% moved outside the service areas of the programs. Although a higher proportion of blacks (to whites) moved within the service areas, a similar proportion moved outside the service areas. This low residential mobility, especially the low rate of movement outside the service areas of the treatment centers, suggests that mobility of cohorts under long-term treatment and observation may present lesser problems to continuous, long-term community health care programs than do other factors affecting adherence.

Clinical experience with guanfacine in long-term treatment of hypertension. Part II: adverse reactions to guanfacine.

British Journal of Clinical PharmacologyVolume 10, Issue S1 p. 157S-164S Free Access Clinical experience with guanfacine in long-term treatment of hypertension. Part II: adverse reactions to guanfacine. P. Jerie, P. JerieSearch for more papers by this author P. Jerie, P. JerieSearch for more papers by this author First published: February 1980 https://doi.org/10.1111/j.1365-2125.1980.tb04924.xCitations: 22AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References AMERY, A.K.P.C., BOSSAERT, H., FAGARD, R.H. & VERSTRAETE, M. (1972). Clonidine versus Methyldopa: A double blind cross-over study comparing side effects of clonidine and methyldopa administered together with chlorthalidone at a dosage producing the same blood pressure lowering effect. Acta Cardiol., 27, 82– 99. ARNOLD, O.H. (1971). Die medikamentöse Therapie der arteriellen Hypertonie. Internistische Praxis, 11, 451– 455. BEVAN, A., HONOUR, A.J. & STOTT, F.G. (1966). Portable recorder for continuous arterial pressure measurement in man. J. Physiol. Lond., 186, 3P. BULPITT, C.J. & DOLLERY, C.T. (1973). Side effects of hypotensive agents evaluated by a self-administered questionnaire. Br. med. J., 3, 485– 490. DOLLERY, C.T. (1976). Centrally acting alpha-adrenoceptor agonists in hypertension: mechanisms and their role in therapy. Aust. N.Z.J., 6, suppl. 3, 88– 94. DUKES, M.N.G. (1977). Side-effects of Drugs. Annual I pp. v– ix. Amsterdam and Oxford: Excerpta Medica. ESCH, I. (1976). Erste Erfahrungen mit BS 100–141, einer neuen blutdrucksenkenden Substanz. Int. J. clin. Pharmac., 14, 109– 112. GEYSKES, G.G., BOER, P. & DORHOUT MEES, E.J. (1979). Clonidine withdrawal. Mechanism and frequency of rebound hypertension. Br. J. clin. Pharmac., 7, 55– 62. GOLDBERG, A.D., WILKINSON, P.R. & RAFTERY, E.B. (1976). The over-shoot phenomenon on withdrawal of clonidine therapy. Postgrad. med. J., 52, suppl. 7, 128– 134. GOLDBERG, A.D., RAFTERY, E.B. & WILKINSON, P. (1977). Blood pressure and heart rate and withdrawal of antihypertensive drugs. Br. med. J., 1, 1243– 1246. HANSSON, L., HUNYOR, S.N., JULIUS, S. & HOOBLER, S.W. (1973). Blood pressure crisis following withdrawal of clonidine (Catapres, Catapresan), with special reference to arterial and urinary catecholamine levels, and suggestions for acute management. Am. Heart J., 85, 605– 610. JÄÄTTELÄ, A. (1976a). Clinical efficacy of BS 100–141 in essential hypertension: A single-blind pilot study. Eur. J. clin. Pharmac., 10, 69– 72. JÄÄTTELÄ, A. (1976b). Comparison of BS 100–141 and clonidine as antihypertensive agents. Eur. J. clin. Pharmac., 10, 73– 76. JERIE, P. (1980). Guanfacine in long-term treatment of hypertension: Part I: Efficacy and dosage. Br. J. clin. Pharmac., 10, 37– 48S. KIRCH, W. & DISTLER, A. (1978). Anthypertensive effect of N-amidino-2-(2, 6-dichlorophenyl) acetamide hydrochloride: A double-blind cross-over trial versus clonidine. Int. J. clin. Pharmac., 16, 132– 135. McMAHON, F.G. (1978). Management of Essential Hypertension. Mount Kisco, New York: Futura Publishing Company. MANHEM, P. & HÖKFELT, B. (1980). Effect of guanfacine on blood pressure, pulse rate, catecholamines and plasma renin activity in moderate hypertension. Br. J. clin. Pharmac., 10, 109– 114S. MROCZEK, W.J. & DAVIDOV, M.E. (1978). Rebound hypertension after withdrawal of antihypertensive therapy. Clin. Res., 26, 622. PARSONS, W.B. & MORLEDGE, J.H. (1970). Antihypertensive effect of a new imidazoline compound (clonidine) and chlorthalidone, individually and in combination. Am. J. Cardiol., 26, 258– 261. REID, J.L. (1977). Clonidine withdrawal in hypertension: Changes in blood pressure and plasma and urinary noradrenaline. Lancet, i, 1171– 1174. REID, J.L. & ZAMBOULIS, C. (1980). Guanfacine: effects of long term treatment and withdrawal. Br. J. clin. Pharmac., 10, 183– 188S. RÖCKEL, A., SABEL, B. & HEIDLAND, A. (1978). Therapie der essentiellen und renalen Hypertonien mit BS 100–141 (Guanfacinum). Herz/Kreislauf, 10, 136– 142. SEEDAT, Y.K. (1978). Long-term treatment of hypertension with guanfacine (BS 100–141) alone and in combination therapy, Curr. ther. Res., 24, 288– 298. SPACH, M.O., STEIMER, C. & BLOCH, R. (1977). Manifestations cliniques à l'arrêt d'un traitement prolongé par la clonidine. Nouv. Presse méd., 6, 1201– 1205. VETERANS ADMINISTRATION COOPERATIVE GROUP ON ANTIHYPERTENSIVE AGENTS. (1967). Effects of treatment on morbidity in hypertension, I. Results in patients with diastolic blood pressure averaging 115 through 129 mm Hg. J. Am. med. Assoc., 202, 116– 122. WHITSETT, Th.L., CHRYSANT, S.G., DILLARD, B.L. & ANTON, A.H. (1978). Abrupt cessation of clonidine administration: A prospective study. Am. J. Cardiol., 41, 1285– 1290. Citing Literature Volume10, IssueS1February 1980Pages 157S-164S ReferencesRelatedInformation

Acute and long-term effects of labetalol on systemic and pulmonary haemodynamics in hypertensive patients

The effects of the combined adrenergic alpha- and beta-receptor blocking compound labetalol on the systemic and pulmonary circulation were studied after its acute and long-term administration to patients with essential hypertension (WHO grade I–II). Nine men and one woman (mean age 46 years) participated in the acute study. Cardiac index, systemic blood pressure, pulmonary artery pressure and heart rate were measured at rest in the supine and upright positions, and during supine exercise at two work loads (50 and 100 watt), before and after intravenous administration of labetalol 50 mg. Eight of the men were re-examined after three months oral treatment with labetalol 600–900 mg daily. In the acute study cardiac index was unchanged by labetalol, except at the work load of 100 watt, when it decreased by 18.7%. The mean blood pressure decreased under all conditions; 11.6 mm Hg at supine rest, 22.3 mm Hg in the upright position, and by 15.9 mm Hg and 16.9 mm Hg at the two work loads. Heart rate was unchanged at supine rest, but was reduced in the upright position 9,0% and during exercise — at 50 watt by 9.3%, and at 100 watt by 10.3%. Systemic vascular resistance decreased at rest in the supine and upright positions, but not during exercise. The pulmonary artery pressure remained unchanged both at rest and during exercise. In the long-term study cardiac index was unchanged except at the heavy work load, when it decreased by 11.4%. Mean blood pressure was reduced significantly under all circumstances, by 14.6 mm Hg at supine rest, 16.8 mm Hg in the upright positions, and by 13.9 mm and 13.4 mm, respectively, at the two work loads. Heart rate was reduced both at rest 13.6% and during exercise at the two work loads 9.6% and 12.4%. Systemic vascular resistance decreased at rest, but not during exercise. The pulmonary artery pressure were unchanged. Thus, the haemodynamic patterns after acute and long-term administration of labetalol were essentially similar, which suggests that the agent is suitable both for acute and long-term treatment of hypertension, at least from a haemodynamic point of view.

Furosemide Compared With Hydrochlorothiazide

To the Editor.— The recent article by Araoye et al (240:1863, 1978), Furosemide Compared With Hydrochlorothiazide: Long-term Treatment of Hypertension, contains misleading statements, and the conclusions drawn are not supported by the data presented. The abstract gives in a rather categorical fashion the impression that the authors have shown hydrochlorothiazide to be a clearly superior antihypertensive agent. An examination of the article shows that this is certainly not the case. Patients were recruited for this study on the basis of their diastolic blood pressures (BPs) (between 95 and 119 mm Hg). The authors' conclusions of increased efficacy of hydrochlorothiazide over furosemide are based entirely on observations of systolic BP. It may be valid to draw conclusions (if the data analysis had been performed properly) on the effect of these drugs on systolic pressure; it is, however, entirely misleading to make sweeping statements concerning antihypertensive effects when the primary selection criterion

Long-term treatment of hypertension with labetalol.

1 Thirty-two hypertensive patients have been treated with labetalol for periods of up to 7 years. 2 Ten patients observed for 6 years from time of stabilization of dosage, did not show any tolerance to labetalol. 3 Postural and exercise hypotension were not seen in these patients over this prolonged follow-up, although they were seen in other patients given over 2 g labetalol daily.