Subjects heterozygous for genetic loss of function of the thiazide-sensitive cotransporter have reduced blood pressure

Gitelmańs syndrome (GS) is an inherited recessive disorder caused by homozygous or compound heterozygous loss of function mutations of the NaCl cotransporter (NCCT) gene encoding the kidney-expressed NCCT, the pharmacological target of thiazide diuretics. An observational study estimated the prevalence of GS to 19/1,000,000, in Sweden, suggesting that approximately 1% of the population carries one mutant NCCT allele. As the phenotype of GS patients, who always carry two mutant alleles, is indistinguishable from that seen in patients treated with high-dose thiazide diuretics, we aimed at investigating whether subjects carrying one mutated NCCT allele have a phenotype resembling that of treatment with low-dose thiazide diuretics. We screened first-degree relatives of 18 of our patients with an established clinical end genetic diagnosis of GS for NCCT loss of function mutations and identified 35 healthy subjects carrying one mutant allele (GS-heterozygotes). Each GS-heterozygote was assigned a healthy control subject matched for age, BMI and sex. GS-heterozygotes had markedly lower blood pressure (systolic 103.3 +/- 16.4 versus 123.2 +/- 19.4 mmHg; diastolic 62.5 +/- 10.5 versus 73.1 +/- 9.4 mmHg; P < 0.001) than controls. There was no significant difference between the groups either in plasma concentration or urinary excretion rate of electrolytes, however, GS-heterozygotes had higher fasting plasma glucose concentration. Similar to patients being treated with low-dose thiazide diuretics, GS-heterozygotes have markedly lower blood pressure and slightly higher fasting plasma glucose compared with control subjects. Our findings suggest that GS-heterozygotes, the prevalence of which can be estimated to 1%, are partially protected from hypertension through partial genetic loss of function of the NCCT. However, as our study had a case-control design, it is important to underline that any potential effects on population blood pressure and risk of future cardiovascular disease need to be examined in prospective and population-based studies.     

Irbesartan/HCTZ fixed combinations in patients of different racial/ethnic groups with uncontrolled systolic blood pressure on monotherapy

The IrbesartaN/hydroChlorothiazide (HCTZ) bLood pressUre reductionS In diVErse patient populations (INCLUSIVE) trial was a multicenter, prospective, open-label, single-arm study evaluating the efficacy and safety of irbesartan/HCTZ fixed combinations in patients > or = 18 years old with uncontrolled systolic blood pressure (SBP, 140-159 mmHg; 130-159 mmHg for type-2 diabetes mellitus patients) after > or = 4 weeks of antihypertensive monotherapy. This analysis focused on different racial/ethnic subgroups. Treatment was sequential: placebo (4-5 weeks), HCTZ 12.5 mg (two weeks), irbesartan/HCTZ 150/12.5 mg (eight weeks) and irbesartan/HCTZ 300/25 mg (eight weeks). Overall, 515 Caucasians, 191 African Americans and 119 Hispanics/Latinos completing placebo treatment were enrolled. Mean SBP changes from baseline (placebo treatment end) to week 18 were -21.5 +/- 13.8 mmHg for Caucasians, -20.7 +/- 16.5 mmHg for African Americans and -22.9 +/- 13.2 mmHg for Hispanics/Latinos, respectively (p<0.001 for each). Mean diastolic BP (DBP) changes were statistically significant (p<0.001) and similar among racial/ethnic subgroups. By week 18, 70% (95% CI, 66%, 74%) of Caucasian, 66% (95% CI, 59%, 74%) of African-American and 65% (95% CI, 57%, 74%) of Hispanic/Latino patients achieved dual SBP/DBP goal. Treatments appeared to be well tolerated. In conclusion, irbesartan/HCTZ treatment provided SBP/DBP goal attainment in approximately two-thirds of Caucasian, African-American and Hispanic/Latino patients with SBP uncontrolled on antihypertensive monotherapy.     

The antihypertensive effect of captopril in severe essential,renovascular, renal and transplant renovascular hypertension

Summary The acute and long-term (6 months) effects of captopril (C) were studied in 23 patients with previously uncontrolled severe (DBP>120 mmHg) hypertension of different origin: essential (EH)n=10, renovascular (RVH)n=9, and renal (RH)n=4. In addition, four patients were treated with renal transplant artery stenosis and hypertension (TRVH), refractory to conventional therapy. Before treatment supine blood pressure (BP, mmHg) averaged: 205/131 (EH), 204/124 (RVH), 207/132 (RH) and 194/117 (TRVH). All patients received diuretics and other antihypertensive drugs, the dosages of which are expressed in arbitrary equivalent units (U) per day (UD=diuretics; UA=other antihypertensive drugs). Antihypertensive therapy before study:UD: EH 1.6; RVH 1.0;UA: EH 7.3; RVH 5.5. After admission, C dosage was increased from 25 mg to a maximum of 150 mg t.i.d. Antihypertensive treatment was reduced as far as possible. DBP decrease after 25 mg C was related to pretreatment PRA in RVH only. After 3 months of C treatment, BP decreased to 190/116 in EH and 145/89 in RVH (EH vs RVHP<0.01), 158/98 in RH, and 154/90 in TRVH. After 6 months, BP response was maintained in RH and TRVH. BP increased slightly in RVH to 158/102 mmHg, mainly because of impaired renal function in three patients with bilateral renovascular disease. In EH,BP decreased to 167/109, since three non-responders were taken out of the group. After 6 months, EH still received higher dosages of antihypertensive drugs than RVH. Acute and chronic hypotensive effects of C were not significantly correlated. Side-effects occurred in five patients: skin rash and pruritus [2], taste disturbances [1], proteinuria [1], and acute renal failure in one patient with TRVH. In our hands, captopril in combination with diuretics was significantly more potent in severe RVH than in EH. Dosages and side-effects of other antihypertensive drugs could be markedly reduced in most patients, which may improve long-term drug compliance.     

Reduction of blood pressure by treatment with alphacalcidol. A double-blind, placebo-controlled study in subjects with impaired glucose tolerance

Disturbances of calcium or vitamin D metabolism have been suggested to be of pathogenetic importance both for hypertension and impaired glucose tolerance, two disorders that are commonly associated. In the present study 65 men, aged 61-65 years, with impaired glucose tolerance were enrolled in a prospective, double-blind, placebo-controlled study over 12 weeks evaluating the effects of 0.75 microgram alphacalcidol, a synthetic analog to the active metabolite of vitamin D. In the 26 patients with blood pressure greater than or equal to 150/90 mmHg before treatment a significant reduction (p less than 0.01) of both the systolic (SBP) and diastolic (DBP) blood pressure was found after therapy (from 171/95 to 150/88 mmHg). The effect was additive to concomitant antihypertensive treatment and was correlated (p = 0.03) to a reduction of serum levels of parathyroid hormone. Also in the whole group of patients given alphacalcidol blood pressure was moderately lowered from a mean of 152/87 +/- 22/10 (SD) to 143/84 +/- 17/8 mmHg. There were no relationships between the changes in body weight, blood glucose or insulin parameters and the changes in blood pressure during the trial. The findings are compatible with the concept that calcium metabolism influences blood pressure regulation and suggest that supplementation with a physiologic dose of active vitamin D could be beneficial for patients with high blood pressure.     

Effects of alpha-adrenergic receptor blockade on coronary circulation in conscious dogs

The effects of three alpha-adrenergic-receptor blocking agents (phentolamine, prazosin, and trimazosin) were compared on the coronary circulation and left ventricular (LV) function in chronically instrumented conscious dogs. The three alpha-adrenergic-receptor blocking agents were administered in equidepressor doses (mean arterial pressure fell by approximately 20%) and in the presence of beta-adrenergic-receptor blockade and constant heart rate. LV systolic pressure, LV end-diastolic pressure, and LV end-diastolic diameter also fell similarly with the three drugs. Phentolamine decreased the time rate of change of LV pressure (LV dP/dt) by 21 +/- 3%, whereas trimazosin and prazosin decreased LV dP/dt only by 14 +/- 2 and 11 +/- 2%, respectively. LV velocity was not changed with trimazosin and prazosin but decreased with phentolamine by 12 +/- 4%. The three drugs exerted differential effects on the coronary circulation. Only trimazosin increased coronary blood flow (18 +/- 5%). Trimazosin decreased late diastolic coronary resistance (LDCR) by 35 +/- 2%, which was significantly more than reductions in LDCR induced by prazosin (22 +/- 2%) and by phentolamine (11 +/- 3%). A test dose of phenylephrine (5.0 micrograms/kg) increased mean arterial pressure by 53 +/- 3.5 mmHg. After trimazosin, prazosin, and phentolamine, the same dose of phenylephrine increased mean arterial pressure by 24 +/- 2.1, 14 +/- 1.6, and 1.9 +/- 0.6 mmHg, respectively. The response after phentolamine was significantly less than with trimazosin (P less than 0.01) and prazosin (P less than 0.02). Thus the capacity of these three alpha-adrenergic-receptor blocking drugs to dilate coronary vessels is inversely proportional to their capability to block exogenous alpha-adrenergic-receptor agonists.     

Regional hemodynamic effects produced following application of L-glutamic acid to the ventral medullary surface of the cat

The neuronal stimulant L-glutamic acid (GA) was applied to the ventral medullary surface and diastolic arterial blood pressure (DBP), heart rate (HR), renal and femoral arterial blood flow were measured in the chloralose-anesthetized cat. GA (1.0 M) increased DAP by 27 +/- 6.6 mmHg (P less than 0.05, n = 6), but heart rate was not affected (P greater than 0.05). Renal arterial resistance (RR) increased by 15 +/- 5.8% (P less than 0.05) and femoral resistance (FR) increased by 46 +/- 10% (P less than 0.05). The difference in the change in RR and FR was statistically significant (P less than 0.05). These effects were dose-dependent and could be blocked by prior intravenous administration of the alpha-blocker prazosin. These data indicate that neurons in the intermediate area of the ventromedullary surface may have a greater control over femoral flow than renal flow.     

Blood pressure control in treated hypertensive patients: clinical performance of general practitioners.

BACKGROUND: The blood pressure of many treated hypertensive patients remains above recommended target levels. This discrepancy may be related to general practitioners' (GPs') actions. AIM: To assess clinical performance of GPs in blood pressure control in treated hypertensive patients and to explore the influence of patient and GP characteristics on clinical performance. DESIGN OF STUDY: Cross-sectional study conducted on 195 GPs with invitations to participate made via bulletins and by letter. SETTING: One hundred and thirty-two practices in the southern half of The Netherlands from November 1996 to April 1997. METHOD: Performance criteria were selected from Dutch national hypertension guidelines for general practice. GPs completed self-report forms immediately after follow-up visits of hypertensive patients treated with antihypertensive medication. RESULTS: The GPs recorded 3526 follow-up visits. In 63% of these consultations the diastolic blood pressure (DBP) was 90 mmHg or above. The median performance rates of the GPs were less than 51% for most of the recommended actions, even at a DBP of > or = 100 mmHg. Performance of non-pharmacological actions increased gradually with increasing DBP; prescribing an increase in antihypertensive medication and making a follow-up appointment scheduled within six weeks rose steeply at a DBP of > or = 100 mmHg. Patient and GP characteristics contributed little to clinical performance. Action performance rates varied considerably between GPs. CONCLUSION: GPs seem to target their actions at a DBP of below 100 mmHg, whereas guidelines recommend targeting at a DBP of below 90 mmHg.     

Sustained antihypertensive effect of captopril combined with diuretics and beta-adrenergic blocking drugs in patients with resistant hypertension

Ten patients with severe hypertension and unsatisfactory blood pressure control during combined therapy with beta-adrenergic blocking drugs, diuretics, and vasodilators were treated with gradually increasing doses of captopril. Vasodilators were discontinued 24 hours prior to captopril administration. Six patients had essential, two renal, and two renovascular hypertension. Mild renal impairment was observed in four patients. Captopril effectively decreased blood pressure for 3 hours in all patients after the first dose. The antihypertensive effect appeared to be triphasic and was sustained in all but one patient during 12 months of observation. Captopril doses of 25-75 mg t.i.d. were sufficient to achieve acceptable blood pressure control (RR less than or equal to 160/100 mmHg) when given in the above mentioned combination. Side-effects were few and tolerable and discontinuation of captopril was not required.     

Clinical studies and therapeutic trials in systolic hypertension.

A disproportionate increase in SBP over DBP has been recognized for many years as a frequent accompaniment of aging. Initially this was considered to be benign, risk free and potentially dangerous to treat. Study over the years has shown that it is not benign and that antihypertensive therapy can reduce the risks of stroke, myocardial infarction, congestive heart failure and cardiovascular death. Currently, the drugs most widely recommended for this purpose are the thiazide diuretics, long acting dihydropiridine calcium channel antagonists, ACE inhibitors, and beta blocking agents. There may be a special place for nitrates, since these agents are very effective in increasing arterial distensibility--a primary abnormality of the disorder--but a formal study of their effectiveness has not been done. Concern about diastolic hypotension during therapy suggests that treatment to lower the blood pressure in this disorder should be carried out gradually with the aim of reducing the SBP toward normal while avoiding diastolic hypotension.     

坎地沙坦治疗轻中度原发性高血压的临床疗效和安全性研究

目的 评价坎地沙坦酯治疗原发性轻中度高血压的临床疗效和安全性。方法 选择48例轻中度原发性高血压病人通过2周导入期后随机分入试验组和对照组各24例,按双盲、平行临床药理试验方法分别给予坎地沙坦酯和氯沙坦治疗。治疗4周后如不能有效控制血压,则将用药剂量加倍并维持到第8周末。检测患者治疗前和治疗后不同时间的血压、心率以及血常规、尿常规、肝、肾功能。记录用药期间可能发生的不良事件。结果 试验组和对照组降压显效率均为100%,治疗后2周末收缩压(SBP)和舒张压(DBP)均已明显降低。此后血压继续下降,与用药治疗前相比,用药8周末,试验组和对照组SBP分别下降20.3mmHg和16.4mmHg,DBP分别下降16.8 mmHg和16.1 mmHg。试验组1例病人服药期间出现中度头痛,1例病人感轻度胸闷和腹胀。两组血常规、肝、肾功能均正常。结论 坎地沙坦酯治疗原发性轻中度高血压疗效良好、服用安全。     

Long-term effects of captopril and atenolol in essential hypertension

Fifty patients with mild or moderate essential hypertension were randomized (double-blindly) to treatment with either captopril (n = 26) or atenolol (n = 24). Their mean supine diastolic blood pressure after placebo was 100-125 mmHg. The study included an initial dose finding phase (12 weeks) during which the dosages of captopril and atenolol were increased stepwise every second week in order to obtain normotension (supine diastolic blood pressure less than 95 mmHg). Hydrochlorothiazide was added when necessary. During the second phase of the study the patients were followed on active treatment for 2 years. After the initial 12 weeks of active treatment, recumbent and standing blood pressures had fallen significantly both in the captopril group (by 31/20 and 33/19 mmHg, p less than 0.001) and in the atenolol group (by 24/18 and 30/20 mmHg, p less than 0.01 (systolic), p less than 0.001 (diastolic)). The antihypertensive effect was maintained in both groups during long-term treatment. The antihypertensive effect of both agents was potentiated to the same extent by addition of hydrochlorothiazide. Side-effects were few and mild. It can be concluded that both captopril and atenolol are safe and effective antihypertensive drugs.     

Increased excretion of urinary N-acetyl-beta-glucosaminidase in essential hypertension and its decline with antihypertensive therapy

The urinary excretion of N-acetyl-beta-glucosaminidase (NAG) is increased in patients whose renal function is impaired by a variety of kidney diseases, and may provide an index of renal injury. To assess its role in essential hypertension, we measured urinary levels of NAG in 80 subjects with essential hypertension (and no evidence of renal disease) and 30 normal controls. NAG values were measured before therapy and after 3 and 12 months of treatment with diuretics. The mean urinary NAG value (+/- S.D.) for the normotensive subjects was 29 +/- 16 nmol per hour per milligram of urinary creatinine. The median value for the untreated hypertensive subjects was 53, and the mean was 65 +/- 61 (P less than 0.01). Systolic blood pressure was directly correlated with NAG levels, whereas diastolic pressure, age, sex, and race were not. Eighty patients followed for one year attained their ultimate blood-pressure reduction within three months (from a mean of 158/103 mm Hg to one of 138/91 mm Hg; P less than 0.001), whereas the urinary NAG level had not declined significantly at three months (from 60 +/- 43 to 54 +/- 54) but had changed significantly at one year (to 45 +/- 28; P less than 0.01 as compared with the initial value). These data suggest that NAG is frequently elevated in patients with high blood pressure even though there is no other evidence of renal damage, and that it can be reduced by successful antihypertensive therapy.     

Beyond controlling blood pressure in the black patient: metabolic considerations.

Hypertension is highly prevalent among African Americans, who are also more likely than whites to develop end-organ complications of hypertension. Traditional diuretic-based stepcare therapy has successfully reduced such complications of hypertension as stroke, congestive heart failure, and premature death in all populations tested. Prevention of coronary deaths has been less successful. Potentially adverse metabolic effects of thiazide diuretics and some beta-blockers may partially explain the less successful cardiac outcomes. Use of antihypertensive agents lacking adverse metabolic effects but still achieving effective blood pressure control could improve cardiac outcomes while maintaining the benefits achieved with older forms of therapy. Achievement of improved cardiac outcomes is now one of the principal goals of hypertension research and treatment.     

Tailoring antihypertensive drug therapy for the black patient

Blacks experience greater incidence, morbidity, and mortality from hypertension in comparison with whites. Blacks also respond differently to antihypertensive agents. While whites tend to respond in similar fashion to many of the different classes of antihypertensives, blacks consistently have the best response to thiazide diuretics. When a second drug is needed for blood pressure control, there are a number of choices: a beta-blocker, an alpha-beta blocker, an alphablocker, a centrally acting agent, a peripherally acting agent, an angiotensin-converting enzyme (ACE) inhibitor, or a calcium channel blocker. Choosing among these involves considerations of efficacy, likelihood of compliance, and symptomatic and metabolic side effects—all important factors. Clinical experience with the ACE inhibitors, and captopril in particular, has shown the value of adding such a drug to a diuretic regimen, both in terms of controlling blood pressure and reducing metabolic derangements, and subsequently, cardiovascular risk factors. Labetalol, the alpha-beta blocker, and prazosin, the alphablocker, have also produced good results in some studies when combined with a thiazide in black patients.     

Captopril, an orally active converting enzyme inhibitor, in the treatment of primary hypertension. A controlled long-term study with reference to initial plasma renin activity

Captopril (SQ 14 225), an orally active inhibitor of angiotensin converting enzyme, was evaluated in the treatment of primary (essential) hypertension in a placebo-controlled long-term study. In 24 patients allocated to captopril treatment, mean supine BP fell from 174 +/- 18/110 +/- 7 to 151 +/- 22/96 +/- 12 mmHg. Ten patients achieved a supine diastolic BP of less than or equally 90 mmHg with a mean BP fall of 28/22 mmHg after 4 weeks' captopril dose titration (75-450 mg daily). In 14 patients, BP fell 19/9 mmHg. When hydrochlorothiazide (50-100 mg daily) was subsequently added, a total supine BP reduction of 51/20 mmHg was noted. In the placebo control group (n = 16), BP changed +1/-2 mmHg from 171/110 mmHg while addition of hydrochlorothiazide caused a mean supine BP fall of 19/10 mmHg. During long-term follow-up (mean 11.8 months), no resistance to therapy developed. A weak correlation, (p less than 0.05) was seen between pretreatment plasma renin activity and initial captopril-induced BP reduction. However, in patients with clearly defined low renin hypertension, the hypotensive effect of captopril was much less than in patients with higher renin values. Captopril induced a significant decrease in urinary aldosterone excretion, which was partially reversed by addition of hydrochlorothiazide. Observed side-effects were proteinuria (1 case), rash (2 cases) and taste disturbances (3 cases). During long-term follow-up, seven patients have dropped out, four due to side-effects and three because of non-compliance.     

An evaluation of the effects of renal artery stenting in renovascular hypertension

Renal artery stenosis is a common cause (1-6%) of secondary hypertension. Renal artery stenting has recently been employed as an adjunct to antihypertensive medication. We evaluated 92 patients who underwent renal angiography of whom 30 were stented. There was a reduction (p < 0.01) in blood pressure immediately post renal artery stenting--systolic BP from 157 +/- 20 to 140 +/- 21 mmHg and diastolic BP from 81 +/- 13 to 72 +/- 12 mmHg was sustained at 6 months follow up (148 +/- 20/76 +/- 12 mmHg) in the outpatients' clinic. The amount of antihypertensive medication did not differ post stenting--2.7 +/- 1.2 pre vs 2.7 +/- 1.2 drugs post procedure. Renal artery stenting did not provide a 'cure' for any patient with atherosclerotic renovascular hypertension and until the results of randomized studies are known we believe use should be restricted.     

The effects of antihypertensive therapy on left ventricular mass in elderly patients

Left ventricular mass sometimes decreases during treatment of hypertension, but this response is inconsistent and its effects on left ventricular function are unknown. In a six-month randomized trial, we studied the ability of verapamil and atenolol to reduce left ventricular mass in 42 elderly patients with hypertension and the effects of this reduction in mass on cardiac function. The mean blood pressure (+/- SE) decreased in both the group that received verapamil (from 171.4 +/- 3.2/93.0 +/- 2.5 mm Hg to 142.9 +/- 2.8/79.0 +/- 2.0 mm Hg) and the group that received atenolol (from 179.6 +/- 4.6/98.5 +/- 2.4 mm Hg to 148.1 +/- 3.3/83.4 +/- 1.2 mm Hg), but the atenolol-treated patients more frequently required the addition of chlorthalidone to achieve blood-pressure reduction (P less than 0.01). Verapamil resulted in a reduction in the left-ventricular-mass index from 104 +/- 5 g per square meter of body-surface area to 85 +/- 5 g per square meter (P less than 0.01). Atenolol did not produce a reduction in the left-ventricular-mass index (109 +/- 9 g per square meter before treatment vs. 112 +/- 10 g per square meter after treatment). Two weeks after the withdrawal of antihypertensive therapy, blood pressure returned to pretreatment values. Nevertheless, in patients whose left ventricular mass had decreased, two measures of diastolic filling, the peak diastolic filling rate to the peak ejection rate, were significantly higher than before treatment (2.42 +/- 0.2 vs. 3.31 +/- 0.4 [P less than 0.05] and 0.61 +/- 0.03 to 0.85 +/- 0.05 [P less than 0.05], respectively). Diastolic filling was unchanged in the group that had no reduction in left ventricular mass. Cardiac output and the ejection fraction at rest and during mild exercise were unchanged in both groups as compared with baseline values. We conclude that left ventricular mass can be reduced in elderly patients with hypertension and mild ventricular hypertrophy who receive antihypertensive therapy. Reduction occurs more frequently with verapamil than with atenolol therapy, increases diastolic filling, and does not impair systolic function.     

Low-dose antihypertensive treatment with a thiazide diuretic is not diabetogenic. A 10-year controlled trial with bendroflumethiazide

Blood pressure (BP) and metabolic variables were determined initially and after 1, 2, 4, 6 and 10 years' treatment in two groups of hypertensive men (n = 53 each) randomized to bendroflumethiazide 2.5-5 mg/day or propranolol 160-320 mg daily. There was no significant differences in BP or metabolic variables between the two groups at entry. BP was reduced to the same degree by both treatments. Five men in the propranolol group and one man in the thiazide group developed clinically overt diabetes during follow-up. Fasting blood sugar increased slightly but significantly though equally in both groups. Oral glucose tolerance was initially impaired to the same degree in both groups but improved significantly during treatment with both drugs. Fasting insulin increased slightly but to the same degree. While serum potassium decreased significantly in the thiazide group, the total body potassium was unchanged in this group. In the propranolol group, serum potassium rose, while total body potassium decreased significantly. Serum urate increased in both groups, though slightly more during thiazide treatment. One case of gout was found in each group. There was no difference in serum lipids between the two groups. The finding in this long-term trial indicate that in middle-aged men with mild to moderate hypertension a low-dose thiazide diuretic like bendroflumethiazide is as effective and safe an antihypertensive agent as the beta-blocker propranolol is and that it does not induce diabetes. The total clinical picture favors the retention of thiazide diuretics as a first choice drug in hypertension.     

Reversibility of cerebral symptoms in severe hypertension in relation to acute antihypertensive therapy. Danish Multicenter Study

Cerebral symptoms were registered in a multicenter study including 64 patients with severe hypertension, diastolic blood pressure (DBP) greater than or equal to 135 mmHg, and more or less pronounced hypertensive encephalopathy. The symptoms were: headache (70%), dizziness (35%), consciousness disturbances (28%), nausea (27%), paresis (23%), blurred vision (22%), paraesthesia (21%) and vomiting (14%). None had convulsions or coma. Initial treatment was furosemide i.v., and if DBP was greater than or equal to 125 mmHg after one hour, patients were randomized to treatment with either i.v. diazoxide (bolus injections of 75-150 mg) or i.m. dihydralazine (bolus injections of 6-12.5 mg). A gradual fall in blood pressure (BP) was obtained in all three groups. Along with BP reduction a substantial regression of neurological symptoms was registered. After 5 hours only minor cerebral symptoms were present without significant difference between diazoxide and dihydralazine. None developed cerebral complications. The study failed to show a significant correlation between BP reduction and regression of neurological symptoms graded semiquantitatively. Reduction of BP by titration using small repeated bolus injections is recommended, but oral treatment should be considered in the patients who are able to ingest peroral medication in spite of neurological symptoms.