Acute Hypertensive Crises Research Articles

Intensive care management of right ventricular failure and pulmonary hypertension crises.

Pulmonary hypertension (PH), an often unrelenting disease that carries with it significant morbidity and mortality, affects not only the pulmonary vasculature but, in turn, the right ventricle as well. The survival of patients with PH is closely related to the right ventricular function. Therefore, having an understanding of how to manage right ventricular failure (RVF) and acute pulmonary hypertensive crises is imperative for clinicians who encounter these patients. This review addresses the management of these patients in detail, addressing: (a) the pathophysiology of RVF, (b) intensive care monitoring of these patients in the intensive care unit, (c) imaging of the right ventricle, (d) intubation and mechanical ventilation, (e) inotrope and vasopressor selection, (f) pulmonary vasodilator use, (g) interventional and surgical procedures for the acutely failing right ventricle, and (h) mechanical support for RVF.

AIR TEMPERATURE AND OZONE CONCENTRATION AS RISK FACTORS FOR LIFE-THREATENING CARDIOVASCULAR CONDITIONS IN SOUTHERN RUSSIA

Heat waves and increasing tropospheric ozone concentration accompanying global warming are recognized as risk factors for public health. The aim of the study was to assess the associations between atmospheric air temperature, ozone concentration as risk factors for life-threatening cardiovascular conditions in Southern Russia. Methods. An ecological study was performed. The number of ambulance calls (the monthly average for 2017 and daily for January, April, July and October) for acute cerebrovascular conditions, hypertensive crises, and acute myocardial infarction were analyzed. Data on mean daily air temperature was obtained from the weather reports (https://rp5. ru). The ozone concentration was determined by the optical method using an automatic gas analyzer at the environmental monitoring station in the Karadagsky State Nature Reserve. Spearman nonparametric correlation analysis was applied to study associations between the outcomes and the selected environmental conditions. Results. During 2017, the average daily concentration of ozone in the surface layer of the atmosphere exceeded the norm by 50-150 %s. The largest number of significant correlations between all recorded cardiovascular life-threatening conditions and air temperature and ozone concentration was detected in July (0,38 < rs < 0,79; all p-values < 0,05). In other seasons of the year, this correlation was somewhat weaker (0,43 < rs < 0,47; all p-values < 0,05). Associations between hypertensive crises and myocardial infarction and average daily temperature were found in January. An association between myocardial infarction and the surface ozone concentration was observed in October. Conclusion. The maximum number of emergency conditions occurring in the summer months may be associated with the synergistic effects of of high levels of ozone and air temperature.

The determinants of neurological phenotypes during acute hypertensive crises – a preliminary study

ABSTRACT Background and Purpose: Acute blood pressure elevations lead to wide spectrum of neurologic manifestations, ranging from no overt neurologic symptoms to catastrophic events like ICH. Little is known regarding the determinants of this clinical variability. We determined clinical and imaging features of hypertensive crisis patients with normal neurological examination, ICH and posterior reversible encephalopathy syndrome (PRES). Methods: Cranial MRI was performed in patients with hypertensive urgency or emergency but normal neurological examination. Their clinical characteristics, and imaging features regarding cerebral small vessel disease were compared to ICH and PRES patients. Results: Hypertensive ICH patients (n = 58) were older, less likely to have hyperlipidemia, less commonly used calcium channel blockers, and had higher burden of chronic cSVD features in comparison to hypertensive crisis patients with normal neurological findings (n = 51). Multivariate analyses revealed cSVD burden score (p = 0.003) to be related with ICH, while higher admission blood pressure levels (p < 0.001), hyperlipidemia (p = 0.006) and calcium channel blocker usage (p = 0.005) were more common in patients with normal neurological examination. The PRES (n = 9) group was comprised of younger patients with recent history of hypertension and low burden of cSVD. Conclusions: Hypertensive surge is associated with ICH when cSVD burden is high, probably caused by microvascular dysfunction secondary to long-standing hypertension, while the episode causes no structural damage if this burden is less. Although our observations are exploratory, short term but severe hypertension manifests with PRES possibly due to the absence of adaptive changes.

SUN-345 Safety Analysis of High-Specific-Activity I-131 MIBG (AZEDRA®) in Patients with Iobenguane Scan Positive Cancers

Introduction: Iobenguane scan positive cancers including pheochromocytoma/paraganglioma (PPGL), neuroblastoma, and gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous tumors that arise from neuroendocrine cells. Recently, high-specific-activity I-131 meta-iodobenzylguanidine (HSA I-131 MIBG, AZEDRA®) was approved in the US for treatment of adult and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic PPGL. We present a pooled analysis of all available clinical trials to further assess the safety profile of HSA I-131 MIBG. Methods: 118 patients from four HSA I-131 MIBG clinical trials (NCT00339131; NCT00458952; NCT00874614; NCT00659984) were included in a pooled analysis for safety assessments. Adverse events (AEs), laboratory tests, number and quantity of HSA I-131 MIBG doses, hypertensive events, blood pressure (BP), heart rate, ECG, and AEs of special interest (AESI) were analyzed using descriptive statistics. Results: Gastrointestinal (GI) toxicities, especially nausea and vomiting, were the most common AEs associated with HSA I-131 MIBG. GI toxicities were not reported after dosimetry doses. GI, blood and lymphatic system, and vascular disorders were higher in PPGL than in neuroblastoma after therapeutic dose 1 when compared to therapeutic dose 2. The incidence of potentially clinically significant changes in BP was similar following dosimetric and therapeutic doses and are consistent with the underlying hypertension associated with PPGL. No spike in systolic and diastolic BP was observed within the first 4 hours of HSA I-131 MIBG administration, and there were no acute hypertensive crises following dosing. A possibly drug-related mild increase in BP within 48 hours of therapeutic dosing was observed in 1 subject with PPGL. Variations in heart rate (>20 beats/min) were higher after therapeutic dose 1 than after other doses. No clinically significant trends were seen in mean ECG results or mean changes from baseline. All patients received at least one concomitant medication. About 40% of patients received β-blockers, 39% α-blockers, and about 27% other peripheral vasodilators. 87.3% of patients reported an AESI, defined as AEs that are related to the acute and/or chronic effects of radiation toxicity seen any time post dosing. The most common AESIs were nausea (66.1%), thrombocytopenia (50.0%), fatigue (50.0%), neutropenia (42.4%), and diarrhea (22.9%). The incidence of most AESIs were similar after each therapeutic dose. Conclusions: HSA I-131 MIBG demonstrated a favorable safety profile in iobenguane scan positive cancers. AEs followed an expected pattern comparable to other radioactive therapeutic agents. Most cardiovascular events, including hypertensive events mostly commonly observed in PPGL, were not considered related to HSA I-131 MIBG.

Abstract TP322: Small Vessel Disease Burden Alters the Clinical Phenotype of Acute Hypertensive Crises

Background: Acute elevations in systemic blood pressure are associated with a wide array of manifestations involving the central nervous system, ranging from no overt neurologic symptoms or signs to catastrophic scenarios like intracerebral hemorrhage (ICH). Very little is known regarding the determinants of this clinical variability. In this study we determined clinical and imaging features of neurologically asymptomatic hypertensive crisis patients, patients with hypertensive ICH and hypertensive posterior reversible encephalopathy syndrome (PRES). Methods: Magnetic resonance imaging (MRI) data was prospectively collected from a consecutive series of patients admitted to the emergency department with a diagnosis of hypertensive urgency or emergency but no neurologic symptoms. Features of small vessel disease (lacunes, microbleeds, perivascular spaces, white matter hyperintensities) were rated and small vessel disease burden score was determined. These features, together with clinical characteristics, were compared to those of patients presenting with hypertensive ICH and PRES. Results: Patients with hypertensive ICH (n=58) comprised the group with the oldest age, longest duration of hypertension and highest burden of vascular risk factors, while the PRES group (n=9) signified the youngest group with short duration of hypertension and minimum number of vascular risk factors. The neurologically asymptomatic hypertensive crisis group (n=51) showed an intermediary phenotype not only with respect to these clinical characteristics, but also in terms of small vessel disease features. Multivariate analyses revealed advanced age (p=0.009), cerebral microbleeds (p&lt;0.001) and small vessel disease burden (p=0.019) to be related with cerebral hemorrhage rather than asymptomatic hypertensive crisis or PRES. Conclusion: The clinical phenotype in the setting of an acute hypertensive episode depends on specific clinical and imaging features. PRES occurs in young brains not accustomed to chronic hypertension, while the episode results in ICH in old patients with a high small vessel disease burden and remains asymptomatic among patients devoid of such characteristics.

The Impact of Targeted Therapies for Pulmonary Hypertension on Pediatric Intraoperative Morbidity or Mortality

Pulmonary hypertension (PHT) is a significant risk factor for major adverse events during anesthesia, with a reported incidence of 5% to 7%, secondary to acute pulmonary hypertensive crises or right ventricular ischemia. Newer therapies for treating PHT have reduced mortality. In this single-center study, we investigated the frequency of major and minor events during anesthesia under the current strategies to manage PHT. We reviewed the records of children with PHT who underwent noncardiopulmonary bypass procedures from 2008 to 2012. Clinically important symptoms, physical signs, and results of investigations present before anesthesia were recorded. The incidence and type of intraoperative complications and death (up to 7 days) were collected. Data were collected for 122 patients undergoing 284 procedures. Minor (3.9%) and major (3.2%) complication rates were unchanged from previous publications. The etiology of PHT was not significant for complications (P = 0.14). Disease-modifying agents were not associated with reduced complications: 4.1% in treated versus 8.6% untreated (all P > 0.14). Patients receiving home oxygen had more complications (P = 0.02). Multiple logistic regression identified age and degree of PHT as significant predictors of complications (all P ≤ 0.03). The risk for adverse events during anesthesia in patients with PHT remains high, despite newer disease-modifying treatments. Risk factors for complications include age and severity of PHT.

Sodium Nitroprusside and Acute Psychosis in the Emergency Department

Sodium nitroprusside (SNP) has been used clinically for the treatment of severe hypertension since 1929 (1). Having vasodilatory effects on both arterioles and venules, it is available for intravenous administration in cases of acute hypertensive crises. Furthermore, this medication has been used in different fields of medicine such as esophageal varices (2), severe pyrexia (3), lactic acidosis (4), neuroleptic malignant syndrome (5), and cerebral vasospasm (6). Adverse effects of SNP usage include bradyarrythmias, tachyarrhythmias, hypotension, restlessness, confusion, and a less common yet dreaded complication, cyanide and thiocyanate toxicity. SNP is known to produce nitric oxide in the brain, increase cGMP production, and modulate NMDA receptor activity (7). Although the precise underlying mechanism remains unclear, SNP is able to halt psychosis-like behaviors. Consequently, low-dose SNP over the course of four hours was recently proposed as a treatment for acute psychosis (8). Administration of SNP as an effective adjuvant therapy for acute psychosis in the emergency departments, despite being novel and attractive, does require further attention and considerations. When used in combination with other psychiatry drugs, which have potential to decrease blood pressure, SNP administration might be associated with decrease in blood pressure and instability in hemodynamics even at low recommended doses. The main characteristic of SNP is hypotension; hence, if physicians opt for SNP administration for the treatment of acute psychosis, the emergency department setting does not seem to be an appropriate environment. It would be more logical to use SNP in ICU settings with closer hemodynamic monitoring and to have more appropriate information on the fluid status, central venous pressure, and in situ central venous lines; therefore, if instability occurs following SNP administration, resuscitation of the patients could be performed safely and without any undesirable delays.

Amyotrophic Lateral Sclerosis with an Acute Hypertensive Crises

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder involving the systemic motor neurons, but autonomic nervous function is relatively well preserved. A few studies related to autonomic dysfunction have been reported, but autonomic dysfunction is rare in ALS. Moreover, dysautonomia symptoms are not prominent in patients with ALS. We present a 55-year-old male patient with ALS, who had acute severe hypertension and tachycardia crises, as well as sudden falls in his blood pressure. After he was diagnosed with ALS, he suddenly collapsed and was placed under mechanical ventilation. Several hypertensive attacks and dysautonomic signs then occurred. We successfully controlled the dysautonomia using diazepam and doxazocin mesylate, an alpha receptor antagonist.

Coronary emergency and diabetes as manifestations of pheochromocytoma

We report on a woman with refractory hypertension and diabetes suffering from hypertensive crises, one with chest pain suggesting acute coronary syndrome, and another with an abdominal pain, after which a para-aortic abdominal mass was diagnosed, by ultrasound, as pheochromocytoma, later confirmed by an adrenal scintigraphic study with 131I-labeled metaiodobenzylguanidine. The patient was successfully treated with complete reversal of hypertension and diabetes. Our case illustrates the importance of maintaining a high index of suspicion in patients simultaneously presenting with an acute myocardial event and hypertensive crises.

EXOGENOUS ESTROGEN RAPIDLY ATTENUATES PULMONARY ARTERY VASOREACTIVITY AND ACUTE HYPOXIC PULMONARY VASOCONSTRICTION

Chronic estrogen exposure has been shown to affect pulmonary artery (PA) vasoreactivity. However, the immediate effects of exogenously administered 17beta-estradiol (E2) on vasopressor-induced PA vasoconstriction and acute hypoxic pulmonary vasoconstriction (HPV) have not yet been investigated. We hypothesized that exogenously administered E2 attenuates PA vasoreactivity and acute HPV through a rapid mechanism. Isometric force displacement was measured in isolated PA rings from proestrus female adult Sprague-Dawley rats, estrus, metestrus, or diestrus female adult Sprague-Dawley rats, and male adult Sprague-Dawley rats. The vasoconstrictor response in the absence of hypoxia (organ bath bubbled with 95% O2/5% CO2) was measured after stimulation with 1 microM of phenylephrine. Hypoxia was generated by changing the gas to 95% N2/5% CO2. The E2 was added to the organ bath in 0.1-nM, 0.5-nM, 1-microM, 500-microM, and 1-mM doses. The 1-mM dose caused an immediate decrease in force in PA rings from estrus, metestrus, or diestrus female adult Sprague-Dawley rats. In addition, 500 microM and 1 mM of E2 attenuated phenylephrine- and hypoxia-induced vasoconstriction and potentiated the vasodilatory phase of hypoxia. These effects were immediate and independent of sex or estrous cycle. Lower E2 doses did not mediate any significant effects. We conclude that high doses of exogenous E2 acutely attenuate PA vasoreactivity and acute HPV in a rapid and dose-dependent manner. A better understanding of how E2 modulates the pulmonary vasomotor response may allow for future therapeutic interventions in acute pulmonary hypertensive crises or in pulmonary arterial hypertension.

Cardiopathia fantastica: the cardiac variant of Munchausen syndrome.

Munchausen syndrome is a rare condition in which the patient repeatedly seeks medical care for factitious illnesses. Cardiac Munchausen syndrome was first reported in 1953 and later referred to as cardiopathia fantastica. It is characterized by clinical manifestations of acute cardiac disease that are feigned and recurrent. Cardiopathia fantastica can have a variety of presentations similar to true cardiac disease. Most cases have presented with chest pain simulating acute coronary artery disease, but arrhythmias, hypertensive crises, abnormal biochemistry, and electrocardiographic findings have also been noted. These patients are willing to undergo expensive, invasive, and risky procedures to evaluate their simulated illness. This condition is likely to be significantly underreported. In some patients, the presence of abnormal findings that are clinically insignificant may complicate the investigative approach. Patients with this disorder consume a disproportionate amount of health care dollars and sometimes are left with residual deficits as complications of invasive procedures. In this review, we discuss the recognition, manifestations, and treatment of cardiopathia fantastica.

Inhaled nitric oxide versus prostacyclin in chronic shunt-induced pulmonary hypertension

Objective Cardiac surgery for congenital heart defects is commonly complicated by shunt-induced chronic pulmonary hypertension and associated acute hypertensive crises. To investigate the effects of vasodilators in chronic and acute pulmonary hypertension, we used the innominate artery to create a growing aortopulmonary shunt in young piglets. Methods Pulmonary hemodynamics and right ventricular function and their responses to hypoxia, intravenous prostacyclin, and inhaled nitric oxide were investigated after closure of the shunt by using pulmonary flow-pressure relationships, pulmonary vascular resistance partitioning, pulmonary vascular impedance, and ventriculoarterial coupling expressed as the ratio of right ventricular end-systolic elastance to effective pulmonary arterial elastance. Results Shunt-induced pulmonary hypertension was associated with medial hypertrophy of pulmonary arteries, increased resistance, increased elastance, increased wave reflection, and preserved ventriculoarterial coupling. Hypoxic pulmonary vasoconstriction was blunted in the shunt group. Compared with prostacyclin, inhaled nitric oxide was a more effective vasodilator in the shunt group and in hypoxia. Effective pulmonary arterial elastance and right ventricular end-systolic elastance increased in chronic (shunt) and acute (hypoxic) hypertension and decreased with vasodilators, preserving a normal coupling. Conclusions A growing aortopulmonary shunt in the young pig is a reliable model of chronic pulmonary hypertension, with medial hypertrophy, increased resistance, and increased elastance. In this model inhaled nitric oxide is a better pulmonary vasodilator than intravenous prostacyclin, with neither drug having a specific inotropic effect, and normal coupling is preserved in chronic and acute pulmonary hypertension.

Adenosine triphosphate-magnesium chloride: relevance for intensive care.

Despite aggressive resuscitation shock often results in multiple-organ failure characterized by increased energy demands of organs and decreased ability of effective energy production. The administration of ATP-MgCl(2) as a supportive measure has been investigated in various animal models of ischemia/reperfusion injury and hemorrhagic, endotoxic, and septic shock. These studies showed improvement in organ blood flow, microcirculation, energy balance, cellular and mitochondrial, functions and restoration of immune competence, ultimately leading to increased survival. Originally these effects were attributed to direct energy provision by the ATP-Mg complex, but the minute amount of ATP infused compared to the body's ATP formation rate suggests that other mechanisms must be responsible for its beneficial properties such as stabilization of the cell membrane, phosphorylation of membrane proteins, decreased cell swelling, and improved microcirculatory perfusion. The experimental evidence currently available suggests the use of ATP-MgCl(2) as a therapeutic adjunct in patients with multiple-organ dysfunction. In addition, given the extremely short half-life which allows both rapid titration and control of the systemic hemodynamic response, for example, reduction in mean arterial pressure, ATP-MgCl(2) may be suitable as an alternative to other fast-acting vasodilators used for the management of acute pulmonary hypertensive crises and/or for the maintenance blood pressure during aortic cross-clamping.

Acute hypertensive crises in children: emergencies and urgencies.

Hypertensive crises result from acute elevations in blood pressure. Although uncommon in children, they can be life-threatening and require immediate recognition and treatment to decrease morbidity. The diagnosis is made following complete history and physical assessment, with confirmation of blood pressure elevation using an appropriate-size blood pressure cuff. There are various options for treatment. Some of the more commonly used agents include nitroprusside, diazoxide, hydralazine, labetalol, esmolol, nicardipine, nifedipine, enalaprilat, and minoxidil. Close monitoring of blood pressure during treatment is mandatory to ensure a good outcome.

Ectopia lentis et pupillae syndrome in three generations.

In nine members from three generations and in a distant relative, at least three significant characteristics of the ectopia lentis et pupillae syndrome were established including ectopia lentis, ectopia pupillae, persistent pupillary membrane, iris transillumination, and poor pupillary dilatation. All patients developed bilateral cataract before the age of 40 years, and two patients presented with intermittent acute intraocular hypertensive crises. Not only the high number of patients in one family, but also the occurrence in three generations is very exceptional for the ectopia lentis et pupillae syndrome. Although the syndrome is said to be inherited in an autosomal recessive mode, in this family, a mother to son and a mother to daughter transmission were present. Pedigree analysis yielded arguments in favour of an autosomal dominant inheritance with reduced penetrance. A biochemical correlation was not identified.

Veno-Venous Extracorporeal Membrane Oxygenation with A Heparin-Coated System in Adult Respiratory Distress Syndrome

Three patients with adult respiratory distress syndrome were treated with veno-venous extracorporeal membrane oxygenation, ECMO, using a heparin-coated system for 8, 12 and 34 days, respectively. Despite extracorporeal blood flow of 4-5 l/min, the patients were ventilator-dependent in the initial period of ECMO. Two of the three patients showed bleeding diatheses despite only slightly elevated activated partial thromboplastin time (APTT). Blood platelet count followed a variable course and serum fibrinogen was normal. Acute pulmonary hypertensive crises, fatal systemic infection, recurrent pneumothorax and plasma leakage from the oxygenators were other main complications during ECMO. Two of the three patients survived, and follow-up showed that severely damaged lungs, if supported in the acute phase, can recover sufficiently to permit normal living.

Psychiatric aspects of congestive heart failure: implications for consulting psychiatrists.

Abnormalities of mental function are common problems in patients with congestive heart failure, a problem that is often referred to the consulting psychiatrist. These abnormalities become more frequent and more serious as failure of the heart progresses and they can exhibit a wide variety of manifestations. Cardiac output and cerebral blood flow are preserved due to compensatory mechanisms in mild heart failure but can be severely compromised in advanced failure. Drugs used to treat heart failure, especially digitalis, can produce a wide variety of mental aberrations including delirium, usually when these drugs are used in excess. Diuretics can produce electrolyte abnormalities resulting in mental derangements and vasodilator therapy can produce hypotension. Psychotropic drugs are well recognized as having significant cardiovascular effects that need to be considered when these agents are applied to the cardiac patient. Antidepressant and antipsychotic drugs have anticholinergic, antiadrenergic and quinidine-like effects that can produce further cardiac decompensation in heart failure. Antidepressants are generally well tolerated except when toxic levels occur or in the most extremely compromised cardiac patients. Monoamine oxidase inhibitors should be used only in highly reliable patients to avoid the acute hypertensive crises that are well known to occur with these agents. Antipsychotic drugs with limited cardiovascular side effects can be used effectively and safely but care must be taken to avoid toxic levels which could produce excess hypotension or lethal arrhythmias. Lithium can also be used in heart failure if patients are effectively monitored to avoid toxic levels which could occur due to reduction in renal function, use of diuretics or imposition of a low sodium chloride diet. Evaluation and management of patients with mental symptoms and heart failure provides a strong challenge for the consulting psychiatrist.

Mechanism of action of calcium antagonists in heart and vascular smooth muscle.

A transmembrane supply of Ca2+ ions is required for active tension development in both vascular smooth musculature and myocardial fibres. Ca2+ antagonists thus not only damp hyperkinetic myocardial dysfunction but also act against practically all vasoconstrictor or spastic responses of extramural coronary smooth muscle. Clinically important targets of Ca2+ antagonists include the pulmonary, cerebral, mesenteric and renal arteries, as well as the peripheral resistance vessels of the systemic circulation. Ca2+ antagonists are used increasingly to treat acute hypertensive crises as well as for long-term antihypertensive therapy. In physiological experiments, Ca2+ antagonists not only neutralize various vasoconstrictor agents but also greatly reduce the sensitivity of the systemic arteries and arterioles to mechanical stimuli such as extension of the vascular wall by a rise in intraluminal pressure. In human arterial walls, at an advanced age, cytotoxic degrees of Ca2+ overload probably play an important role in the pathogenesis of arteriosclerotic lesions. Severe diabetics and heavy smokers exhibit an even faster progression of age-dependent arterial calcinosis. In rats, the Ca2+ antagonist verapamil not only prevented arterial calcinosis due to overdoses of vitamin D and dihydrotachysterol but also counteracted age-dependent Ca2+ accumulation. Spontaneously hypertensive rats also exhibit progressive arterial Ca2+ overload which responds excellently to the Ca2+ antagonists nifedipine, nimodipine, nisoldipine, nitrendipine, as well as to verapamil and diltiazem. Suitable Ca2+ antagonists could possibly retard or even prevent premature arterial calcinosis in humans. Moreover, Ca2+ antagonists exert a direct cardioprotective effect on the myocardium by preventing intracellular Ca2+ overload.

Comparison of Sublingual Captopril and Nifedipine in Hypertensive Crises

To the Editor. —The recent demonstration by Tschollar and Belz1that treatment of hypertensive crises with sublingual captopril induces a safe and rapid lowering of blood pressure (BP) suggests the need for prospective studies clinically comparing sublingual captopril with nifedipine. In the first comparative study, Hauger-Klevene2concluded that the hypotensive effect of sublingual nifedipine therapy occurs earlier but has a shorter duration than that of sublingual captopril. In a randomly conducted, doubleblind study, we compared the hypotensive effect of sublingual captopril and nifedipine in 50 consecutive patients with acute hypertensive crises treated in a hospital emergency room. All patients had essential hypertension and a mean BP higher than 130 mm Hg in two different measurements five minutes apart. Equiparable captopril or nifedipine powder capsules for clinical investigation were prepared in the pharmacy department. We administered to each patient an initial capsule, containing either 25 mg of captopril or

Antihypertensive and arterial anticalcinotic effects of calcium antagonists

In vascular smooth muscle (as in myocardial fibers), a transmembrane supply of calcium ions is required for active tension development. In consequence, calcium antagonists possess a wide scope of action against practically all types of vasoconstrictor or spastic responses of arterial smooth muscle cells. Calcium antagonists are the drugs of choice for the treatment of coronary, pulmonary, cerebral or mesenteric artery spasms. Other clinically important targets of calcium antagonists are the systemic resistance vessels that rapidly dilate, which explains why calcium antagonists are increasingly used for the treatment of acute hypertensive crises as well as for antihypertensive long-term therapy. In physiologic experiments, calcium antagonists normalize the blood pressure of spontaneously hypertensive rats, neutralize various vasoconstrictor agents (if they act via promotion of transmembrane calcium influx), and greatly reduce the sensitivity of the systemic arteries and arterioles to mechanical stimuli, which can produce additional vasoconstriction, if a rise in intraluminal pressure stretches the vascular wall (Bayliss effect). Calcium antagonists also prevent noxious arterial calcium overload in animals. In the human arterial walls, at an advanced age, pathogenic degrees of calcium accumulation are reached and probably play an important role in both the development of hypertension and of arteriosclerotic lesions. Hypertensive rats exhibit progressive arterial calcium overload that responds well to the calcium antagonists nifedipine, nimodipine, nisoldipine and nitrendipine, as well as to verapamil.