Hypertensive emergencies and urgencies: Pathophysiology and clinical aspects

A hypertensive urgency should be distinguished from a hypertensive emergency. Although the distinction may not always be obvious, certain guidelines may help the clinician determine which therapeutic approaches are most appropriate for each patient. Hypertensive emergencies include those conditions in which new or progressive severe end-organ damage is present and a delay in appropriate therapy might result in permanent damage, progression of complications, and a poor prognosis. Hypertensive urgencies include those conditions with minimal to no obvious end-organ damage in which blood pressure should be lowered expeditiously. The risk of immediate complications or organ damage is less likely to occur, and thus the immediate prognosis is better, although the ultimate prognosis, if untreated, is poor. There is a marked individual, racial, sexual, and age difference in the ability to tolerate high intraarterial pressure, as evidenced by patients' symptoms and signs of end-organ damage.Patients may have no symptoms of elevated blood pressure until significant intraarterial levels are reached. If symptoms are present, they may include headache, dizziness, blurred vision, shortness of breath (especially with exertion), chest pain, rapid pulse, palpitations, malaise and fatigue, nocturia, or pedal edema.^7,11–14 Signs of hypertensive disease vary and depend not only on the level of blood pressure but also include funduscopic changes with arteriolar narrowing, atrioventricular nicking, hemorrhages, exudates or papilledema, central nervous system changes and neurologic abnormalities, cardiac changes with gallop rhythm, cardiomegaly, tachycardia, ectopic ventricular beats, left ventricular hypertrophy or signs of congestive heart failure, pulmonary edema, and signs of renal insufficiency.^7,11–14Although there is a definite correlation between the level of blood pressure and end-organ damage, there is no definite systolic or diastolic level of blood pressure that induces end-organ damage. Some patients may tolerate very high blood pressures with few symptoms or signs, whereas others may manifest end-organ damage at lower blood pressures. Thus, the definition of hypertensive emergency and urgency depends on the clinical assessment of the blood pressure level and clinical and laboratory assessments of end-organ damage. The absolute blood pressure in itself does not determine the seriousness of the clinical situation, the expediency of treatment, or the need for in-hospital monitoring in a critical care unit.It is important not to lower the blood pressure precipitously or to a subnormal level particularly in patients with end-organ damage. Such treatment may critically reduce blood flow and perfusion to vital organs and induce a cerebrovascular accident, myocardial ischemia, or renal failure. A smooth, gradual reduction in blood pressure is crucial to patient management with oral or parenteral antihypertensive drugs. However, in hypertensive emergencies blood pressure control should be accomplished within 1 hour, whereas with hypertensive urgencies control should be within 24 hours.Those patients who have hypertensive emergencies with malignant hypertension and end-organ damage should be admitted to a hospital intensive care unit for evaluation and treatment. These patients have a diffuse arteritis, as of a result of their hypertension, that may take 4 to 6 weeks to heal. Many patients who present with diastolic blood pressure 120 mm Hg or greater will be found to have a secondary cause of hypertension (such as renovascular hypertension) after careful evaluation. On the other hand, those patients with hypertensive urgencies as defined previously can be treated in the emergency room or outpatient department and can avoid hospital admission. Careful, immediate, and routine follow-up is important in these patients.     

Emergency Room Management of Hypertensive Urgencies and Emergencies

Hypertensive crisis affects upward of 500,000 Americans each year. Although the incidence of hypertensive crisis is low, affecting fewer than 1% of hypertensive adults, more than 50 million adult Americans suffer from hypertension. Presentation of a patient with severe hypertension to the emergency room demands immediate evaluation, prompt recognition of a hypertensive emergency or urgency, and the prompt institution of appropriate therapeutic measures to prevent progression of target-organ damage and to avoid a catastrophic event. Hypertensive emergencies are severe elevations in blood pressure that are complicated by evidence of progressive target-organ dysfunction such as coronary ischemia, disordered cerebral function, a cerebrovascular event, pulmonary edema, or renal failure. Although therapy with parenteral antihypertensive agents may be initiated in the emergency department, these patients warrant prompt admission to an intensive care unit where continuous monitoring of blood pressure can be assured during therapy.     

Dutch guideline for the management of hypertensive crisis -- 2010 revision

Hypertensive crises are divided into hypertensive urgencies and emergencies. Together they form a heterogeneous group of acute hypertensive disorders depending on the presence or type of target organs involved. Despite better treatment options for hypertension, hypertensive crisis and its associated complications remain relatively common. In the Netherlands the number of patients starting renal replacement therapy because of 'malignant hypertension' has increased in the past two decades. In 2003, the first Dutch guideline on hypertensive crisis was released to allow a standardised evidence-based approach for patients presenting with a hypertensive crisis. In this paper we give an overview of the current management of hypertensive crisis and discuss several important changes incorporated in the 2010 revision. These changes include a modification in terminology replacing 'malignant hypertension' with 'hypertensive crisis with retinopathy and reclassification of hypertensive crisis with retinopathy under hypertensive emergencies instead of urgencies. With regard to the treatment of hypertensive emergencies, nicardipine instead of nitroprusside or labetalol is favoured for the management of perioperative hypertension, whereas labetalol has become the drug of choice for the treatment of hypertension associated with pre-eclampsia. For the treatment of hypertensive urgencies, oral administration of nifedipine retard instead of captopril is recommended as first-line therapy. In addition, a section on the management of hypertensive emergencies according to the type of target organ involved has been added. Efforts to increase the awareness and treatment of hypertension in the population at large may lower the incidence of hypertensive crisis and its complications.     

How should we treat a hypertensive emergency?

Hypertensive emergencies are life-threatening situations caused by acute blood pressure elevation. They require immediate treatment with antihypertensive drugs. Such emergencies include hypertensive crisis, acute left ventricular heart failure or intracranial bleeding in patients with hypertension, malignant hypertension resistant to treatment, and serious blood pressure elevations after vascular surgery. A hypertensive crisis may be defined as a sudden increase in systolic and diastolic blood pressure that causes functional disturbances of the central nervous system, the heart or the kidneys. In patients with hypertensive crisis, treatment should be started with an alpha receptor-blocking agent if pheochromocytoma has not been excluded by previous workup. Antihypertensive agents with a rapid onset of action--nifedipine, clonidine, dihydralazine, diazoxide and sodium nitroprusside--are being used.     

Hochdruck und hypertensiver Notfall in der Schwangerschaft

BACKGROUND: Hypertensive emergencies are acute, life threatening, and usually--but not necessarily--associated with severe increases in blood pressure. In pregnancy, this is the fact in eclampsia. Eclampsia refers to the occurrence of one or more generalized convulsions in the setting of preeclampsia with proteinuria, edema, and hypertension. PATHOGENESIS: Our current understanding of the pathogenesis of preeclampsia will be reviewed here. Some major risk factors for the development are preexisting hypertension and renal disease. PREVENTION AND THERAPY: Preventive measures of preeclampsia and treatment of this specific hypertensive emergency in pregnancy are discussed.     

Treatment of hypertension based on measurement of blood pressure variability: lessons from animal studies

PURPOSE OF REVIEW: Blood pressure variability, a quantitative index for the spontaneous variation in blood pressure, has been proposed as a risk factor for end-organ damage and to determine the efficacy of hypertension treatment. RECENT FINDINGS: Animal studies indicate that blood pressure variability is as important as blood pressure level in determining end-organ damage, and that high blood pressure variability is associated with end-organ damage, including myocardial lesions, aortic hypertrophy, vascular remodeling and renal damage. Although the organ damage induced by high blood pressure variability was similar to that induced by hypertension, comparative studies in sinoaortic-denervated and spontaneously hypertensive rats revealed that aortic hypertrophy is a sensitive index of high blood pressure variability, and left ventricular hypertrophy is a sensitive index of high blood pressure level. The possible mechanisms for high blood pressure variability-induced end-organ damage include: direct endothelial lesions, renin-angiotensin system activation, inflammation initiation and cardiomyocyte apoptosis augmentation. Blood pressure variability reduction contributes importantly to the organ-protective effect of some antihypertensive drugs. SUMMARY: Although animal studies suggest some advantages in blood pressure variability measurements, clinical trials are necessary before the widespread use of blood pressure variability as a predictor of hypertensive organ damage and a new strategy for the treatment of hypertension.     

Behandlung des hypertensiven Notfalls

DEFINITION, PATHOPHYSIOLOGY, THERAPY: The hypertensive crisis is characterized by a massive, acute rise in blood pressure. Patients with underlying hypertensive disease usually have an increase in systolic blood pressure values > 220 mmHg and diastolic values > 120 mmHg. The severity of the condition, however, is not determined by the absolute blood pressure level but by the magnitude of the acute increase in blood pressure. Thus, in the presence of primarily normotensive baseline values (such as those in eclampsia), even a systolic blood pressure > 170 mmHg may lead to a life-threatening condition. The most important causes are non-compliance (reduction or interruption of therapy), inadequate therapy, endocrine disease, renal (vessel) disease, pregnancy and intoxication (drugs). The management of this condition greatly depends on whether the patient has a hypertensive crisis with organ manifestation (hypertensive emergency) or a crisis without organ manifestation (hypertensive urgency). By documenting the medical history, the medical status and by simple diagnostic procedures, the differential diagnosis can be established at the emergency site within a very short period of time. In the absence of organ manifestations (hypertensive urgency) the patient may have non-specific symptoms such as palpitations, headache, malaise and a general feeling of illness in addition to the increase in blood pressure. In a hypertensive urgency the patient's blood pressure should not be reduced within a few minutes but within a period of 24 to 48 hours. Such adjustment can be achieved on an out-patient basis, however, only if the patient can be followed up adequately for early detection of a renewed attack. In the absence of follow-up facilities, the patient's blood pressure should be reduced over a period of 4 to 6 hours, if necessary in an out-patient emergency service. While intravenous medication is given preference when a rapid effect is desired, oral medication may be used for gradual reduction on an out-patient basis, depending on the patient's medical history and on any underlying chronic disease. Organ manifestations in the course of a hypertensive emergency concern the cardiovascular system and are associated with the symptoms of acute left-ventricular heart failure, the acute coronary syndrome or acute aortic dissection. In the brain the patient may have symptoms of hypertensive encephalopathy, hemorrhage, ischemia; in the kidney he/she may develop acute failure. The patient's blood pressure should be reduced rapidly during the treatment. It should not be reduced to the normal value, but by approximately 20-30% of the baseline value. The reason for a stepwise reduction in blood pressure is the fact that patients with chronic hypertension have an altered autoregulation curve. Acute normotension would lead to hypoperfusion in these patients. Those with aortic dissection or pulmonary edema are excepted from the rule of gradual blood pressure reduction. In the presence of these diseases, blood pressure must be reduced rapidly to normal values. Patients with a hypertensive emergency should always be admitted to the hospital. Parenteral treatment is given preference, since the effect of the treatment is rapid and occurs within a calculable period of time. Thus, parenteral treatment can also be better regulated than medication administered orally or by the sublingual route. Several antihypertensives are available for this purpose. The selection of the substance greatly depends on the existing organ failure as well as the reliable effectiveness and the regulability of the applied antihypertensive.     

Hypertensive emergencies

Critical cases of high blood pressure are common clinical occurrences that may account for as many as 25% of all medical emergencies. About 75% of these increases in blood pressure can be judged as hypertensive urgencies, 25% are even hypertensive emergency situations. Nevertheless, only less than 1% of the hypertensive population experiences hypertensive urgency or emergency situations. Hypertensive emergencies are defined as acute cardiac, vascular or cerebral target organ damages. In these cases an acute lowering of blood pressure is inevitable. The rate and intensity of blood pressure depression is dependent on the localization of organ damages. For cardiac and vascular damages it is absolutely necessary to lower the blood pressure rapidly to near normal values. On the contrary, cerebral organ damages are better treated by a moderate lowering of blood pressure peaks to slightly increased blood pressure levels. In hypertensive urgencies no target organ damages occur. For these patients a slow lowering of blood pressure values to normal levels is adequate.     

Accelerated arterial hypertension in a young male

Hypertensive crises are situations when arterial hypertension shows its immediate damaging potential, and in such circumstance, antihypertensive therapy provides its life-saving effectiveness. Among these situations are hypertensive emergencies, hypertensive urgencies, hypertensive encephalopathy, and also accelerated-malignant hypertension characterised by the presence of grade 3 or grade 4 Keith-Wagener retinopathy and numerous complications (acute renal failure, heart failure, haemorrhagic brain stroke or acute coronary events). Despite of antihypertensive therapy, the mortality rate of accelerated-malignant hypertension is about 25% after the 5th year. We present the case of a thirty-three years old male, with a five-year history of non-treated hypertension, who develops accelerated- hypertension with heart failure, microangiopathic haemolytic anaemia and renal failure that requires renal replacement therapy. After a strict control of blood pressure; initially using parenteral agents such as Solinitrin and Urapidil, followed by angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-adrenergic receptor blockers, calcium channel blockers and Hydralazine, the patient partially recovers his renal function, resulting in the withdrawal of haemodialysis.     

Clinical features in the management of selected hypertensive emergencies

A hypertensive emergency is a clinical diagnosis that is appropriate when marked hypertension is associated with acute target-organ damage; in this setting, lowering of blood pressure (BP) is typically begun within hours of diagnosis. For hypertensive urgency with no acute target-organ damage, BP lowering may occur over hours to days. A hypertensive emergency may present with cardiac, renal, neurologic, hemorrhagic, or obstetric manifestations, but prompt recognition of the condition and institution of rapidly acting parenteral therapy to lower BP (typically in an intensive care unit) are widely recommended. For aortic dissection, the systolic BP target is lower than 120 mm Hg, to be achieved during the first 20 minutes using a beta-blocker (typically esmolol) and a vasodilator to reduce both shear stress on the aortic tear and the BP, respectively. Otherwise, sodium nitroprusside is the agent with the lowest acquisition cost and longest record of successful use in hypertensive emergencies; however, it is metabolized to toxic thiocyanate and cyanide. Other attractive agents include fenoldopam mesylate, nicardipine, and labetalol; in pregnant women, magnesium and nifedipine are used commonly. Most authors suggest a reduction in mean arterial pressure of approximately 10% during the first hour and a further 10% to 15% during the next 2 to 4 hours; hypoperfusion can result if the BP is lowered too suddenly or too far (eg, into the range of <140/90 mm Hg). Oral antihypertensive therapy can usually be instituted after 6 to 12 hours of parenteral therapy, and the patient moved out of the intensive care unit, when consideration should be given to screening for secondary causes of hypertension. Long-term follow-up to ensure adequate control of hypertension is necessary to prevent further target-organ damage and recurrence of another hypertensive emergency.     

Acute blood pressure increase during the perioperative period

Hypertensive reactions occur frequently in the perioperative setting. Perioperative blood pressure elevation is generally amenable to treatment in previously normotensive patients. Alterations in cerebral autoregulation and myocardial performance in chronic hypertension limit the compensatory range available to cope with perioperative blood pressure changes. In cardiovascular or cerebrally compromised patients, the pathophysiology of underlying disease must therefore be taken into account. In the cerebrally compromised patient with space-occupying lesions and even merely locally impaired cerebral autoregulation, any blood pressure increase may reduce cerebral perfusion pressure and cause further cerebral impairment. Furthermore, vasodilation of cerebral vessels must be avoided to prevent further increase in intracranial pressure with reduction of cerebral perfusion. In chronically hypertensive patients, sufficient preoperative antihypertensive therapy is essential to avoid acute perioperative blood pressure elevation. Before antihypertensive pharmacologic therapy is begun, it is essential to rule out all correctable secondary causes of hypertension, particularly impairment of ventilation and oxygen supply. When pharmacologic antihypertensive therapy is necessary, vasodilators (e.g., calcium entry blockers) may be administered to chronically hypertensive patients. If elevated intracranial pressure is the underlying cause of hypertension, cerebral vasodilation must be avoided and only centrally acting antihypertensive agents such as urapidil should be used for management.     

Hypertensive crisis: hypertensive emergencies and urgencies

Hypertensive crisis is a serious condition that is associated with end-organ damage or may result in end-organ damage if left untreated. Causes of acute rises in blood pressure include medications,noncompliance, and poorly controlled chronic hypertension. Treatment of a hypertensive crisis should be tailored to each individual based on the extent of end-organ injury and comorbid conditions. Prompt and rapid reduction of blood pressure under continuous surveillance is essential in patients who have acute end-organ damage.     

Comprehensive management of hypertensive emergencies and urgencies

Despite advances in chronic hypertension management, hypertensive emergencies and urgencies remain as serious complications. Much of this relates to poor compliance with effective antihypertensive management. Hypertensive emergencies and urgencies can also be seen as the initial manifestations of hypertension in pregnancy and in the perioperative period. Multiple classes of intravenous antihypertensive drugs are available to treat hypertensive emergencies, and specific agents may have an advantage in a given clinical situation. Orally active agents are used to treat hypertensive urgencies, and include clonidine, angiotensin-converting enzyme inhibitors, and labetalol. Most patients respond to drug therapy, but problems may arise related to a rapid normalization of blood pressure.     

Clinical features and management of selected hypertensive emergencies

A hypertensive emergency, defined as an elevated blood pressure with evidence of acute target organ damage, can manifest in many forms, including neurological, cardiac, renal, and obstetric. After diagnosis, effective parenteral antihypertensive therapy (typically, nitroprusside starting at 0.5 microg/kg/min, but some physicians prefer fenoldopam or nicardipine) should be given in the hospital. In general, blood pressure should be reduced about 10% during the first hour and another 15% gradually over 2-3 more hours. The exception is aortic dissection, for which treatment includes a b blocker, and the target is systolic blood pressure <120 mm Hg after 20 minutes. Oral antihypertensive therapy can usually be instituted after 6-12 hours of parenteral therapy. Consideration should be given to secondary causes of hypertension after transfer from the intensive care unit. Because of advances in antihypertensive therapy and management, "malignant hypertension" should be malignant no longer.     

Clinical value of multiorgan damage in hypertensive crises: A prospective follow‐up study

Hypertensive crises are associated with high rates of target organ complications and poor outcomes. A recent shift from the definition of malignant hypertension to hypertension‐multiorgan damage (MOD) contributes to the diagnosis and management of hypertensive crises. Here, we prospectively included 166 adult (≥18 years old) patients with hypertensive crises (blood pressure >180/120 mm Hg). Target organs and causes of hypertension were assessed. Patients who were diagnosed with malignant hypertensive retinopathy, the absence of malignant hypertensive retinopathy but the presence of damage to at least 3 organs, and the absence of both retinopathy and MOD were classified as the malignant hypertension (n = 48), hypertension‐MOD (n = 42), and hypertension without MOD (n = 76) groups, respectively. Patients were followed to evaluate renal and cardiovascular prognoses. At baseline, patients with malignant hypertension had worse renal function, higher level of albuminuria, and more severe microvascular damage than those with hypertension‐MOD. Both had similar proportions of malignant arteriolar nephrosclerosis (83% vs 64%), left ventricular hypertrophy (90% vs 88%), abnormal repolarization (71% vs 60%), and left ventricular dysfunction (12% vs 21%). At the twenty months of follow‐up, both the malignant hypertension and hypertension‐MOD groups had similar blood pressure control rates and proteinuria. Both groups had worse renal outcomes than the hypertension without MOD group (P = .002). Patients with hypertension‐MOD (HR = 0.67, [95% CI: 0.30‐1.46], P = .31) had similar renal event‐free survival than patients with MHT after adjustments of age, sex, blood pressure, and proteinuria control. These results suggest that in hypertensive crises, both malignant hypertension and hypertension‐MOD have impact on adverse renal outcomes.     

Association between hypertensive urgencies and subsequent cardiovascular events in patients with hypertension

OBJECTIVE: To determine whether patients with hypertensive urgency have a higher risk for subsequent cardiovascular events compared with hypertensive patients without this event. METHODS: Overall, 384 patients with hypertensive urgency and 295 control patients were followed up for at least 2 years. Hypertensive urgency was defined as a systolic blood pressure above 220 mmHg and/or a diastolic blood pressure above 120 mmHg without any evidence of acute end-organ damage. The control group consisted of patients admitted to the emergency department with a systolic blood pressure between 135 to 180 mmHg and a diastolic blood pressure between 85-110 mmHg. The number of cardiovascular events defined as acute coronary syndrome, acute stroke, atrial fibrillation, acute left ventricular failure and aortic aneurysm were consecutively analyzed during follow-up. The median follow-up time was 4.2 years (interquartile range 2.9-5.7 years). Twenty-six patients of the urgency group and 23 patients of the control group were lost for follow-up. RESULTS: Overall, 117 (17%) patients had nonfatal clinical cardiovascular events and 13 had (2%) fatal cardiovascular events. The frequency of cardiovascular events was significantly higher in patients with hypertensive urgencies (88 vs. 42; P = 0.005). The Cox regression analysis identified age (P < 0.001) and hypertensive urgencies (P = 0.035) as independent predictors for subsequent cardiovascular events. CONCLUSIONS: Hypertensive urgencies are associated with an increased risk for subsequent cardiovascular events in patients with arterial hypertension.     

Treatment of hypertensive urgencies and emergencies

Although systemic hypertension is a common clinical condition, hypertensive emergencies are unusual in clinical practice. There are some situations, however, that qualify as hypertensive emergencies or urgencies. It is important, therefore, to diagnose these acute conditions, in which immediate treatment of hypertension is indicated. The diagnosis of hypertensive emergencies depends on consideration of the clinical manifestations as well as the absolute level of blood pressure. Manifestations of hypertensive emergencies can be quite profound, but they vary depending on the target organ that is affected. Thus, an accurate clinical diagnosis is necessary to render appropriate therapy. Fortunately, effective drug therapy is available to lower the blood pressure quickly in hypertensive emergencies. Physicians should be familiar with the pharmacologic and clinical actions of drugs in treating hypertensive emergencies. With proper clinical diagnosis, hypertensive emergencies can be successfully treated, and complications can be largely prevented with timely intervention.     

Patients With Hypertensive Crises Who Are Admitted to a Coronary Care Unit: Clinical Characteristics and Outcomes

Patients with hypertensive crises, especially hypertensive emergencies, require immediate admittance to an intensive care unit for rapid blood pressure (BP) control. The authors analyzed the prevalence of hypertensive crisis, the clinical characteristics, and the evolution of patients with hypertensive emergencies and urgencies. Patients were divided into 3 groups according to their BP values: group I, predominant systolic hypertension (≥180/≤119 mm Hg); group II, severe systolic and diastolic hypertension (≥180/≥120 mm Hg); and group III, predominant diastolic hypertension (≤179/≥120 mm Hg). Of all of the patients admitted to a coronary care unit, 538 experienced a hypertensive crisis, which represented 5.08% of all admissions. Hypertensive emergency was predominant in 76.6% of the cases, which corresponded to acute coronary syndrome and acute decompensated heart failure in 59.5% and 25.2% of the cases, respectively. A pattern of predominant systolic hypertension (≥180/≤119 mm Hg) was most commonly observed in the hypertensive crisis group (71.4%) and the hypertensive emergency group (72.1%). The medications that were most commonly used at onset included intravenous vasodilators (nitroglycerin in 63.4% and sodium nitroprusside in 16.4% of the patients). The overall mortality rate was 3.7%. The mortality rate was 4.6% for hypertensive emergency cases and 0.8% for hypertensive urgencies cases.     

Thromboembolism in nonvalvular atrial fibrillation: the answer may be in the ventricle.

Hypertensive emergencies, including hypertensive encephalopathy represents an acute threat to vital organ functions and call for urgent treatment. The intravenous medications currently available for the management of hypertensive emergencies, have significant potential for serious side effects and acute lowering of blood pressure has often been the cause of considerable morbidity and mortality. Nifedipine is known to be effective as an antihypertensive agent and it is widely used in hypertensive emergencies. We studied the efficacy and effective dose of nifedipine in 22 patients (9 females and 13 males; mean age 51) with hypertensive encephalopathy. Nifedipine (20 mg by oral drop) caused a significant fall in diastolic an systolic blood pressure in all patients from 236/121 to 172/96 mmHg after 30 minutes (P less than 0.005, P less than 0.001). Continuous therapy with nifedipine (2-5 mg every 2-3 hours, mean total dose 52 mg/24 h) gave successful control of blood pressure. These data prove that nifedipine can be used as the first-line drug for the treatment of hypertensive crises in patients with hypertensive encephalopathy.     

Chronic treatment with the angiotensin I converting enzyme inhibitor, perindopril, restores the lower limit of autoregulation of cerebral blood flow in the awake renovascular hypertensive rat

Chronic hypertension shifts the lower limit of cerebral blood flow autoregulation to a higher pressure level. Although acute administration of angiotensin converting enzyme inhibitors restores the lower limit of cerebral blood flow autoregulation the chronic effects have not received much attention. We studied the effect of the angiotensin converting enzyme inhibitor, perindopril, on mean arterial pressure, basal cerebral blood flow and cerebral blood flow autoregulation in renovascular hypertensive (two-kidney, one clip model) and normotensive male Wistar rats. Seven weeks after renal artery clipping or sham operation rats received daily intraperitoneal injections of perindopril. The dose was increased from 1 to 8 mg/kg over the first 4 weeks until blood pressure was normalized. Chronic renovascular hypertension caused a marked shift in the lower limit of cerebral blood flow autoregulation but did not alter basal cerebral blood flow. Treatment of hypertensive rats with perindopril normalized blood pressure and restored cerebral blood flow autoregulation. Chronic treatment of normotensive rats with perindopril increased basal cerebral blood flow. In conclusion, chronic treatment of renovascular hypertensive rats with perindopril causes a shift in the lower limit of cerebral blood flow autoregulation towards the value observed in normotensive rats.