Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of the heart in hypertension has finally emerged as a major issue of cardiovascular concern by the clinician, physiologist, pharmacologist, biochemist, and molecular biologist. This discussion provides an overview of the present state of knowledge and current areas of investigation in this active area of broad interest. Generally, these relate to: the active participation of the heart (e.g. hemodynamic, humoral, autocrine/paracrine); the adaptive response of the heart (i.e. hemodynamic); non-hemodynamic relationships (vis-a-vis, age, race, gender, humoral, coexistent disease); and current thoughts on mechanisms of so-called regression of left ventricular hypertrophy. Several antihypertensive classes of compounds are characterized by decreasing cardiac mass and left ventricular wall thicknesses. The angiotensin converting enzyme inhibitors are included among these agents; their physiological effects in producing "regression" are under active study as are the mechanisms responsible for these changes. These concerns are no longer of incidental or theoretical interest but have major impact on selection of antihypertensive therapy and the management of the patient with hypertension. Thus, the heart may participate actively in the pathogenesis and maintenance of the disease; it adapts to the vascular disease hemodynamically; but in this regard the response has both positive beneficial concerns as well as negative implications as an independent risk factor. These latter concerns should be explored in great depth before conclusions are made with respect to the long-term implications of antihypertensive therapy on the heart.
J Mol Cell Cardiol 1989 Dec
PMID:Overview of hemodynamic and non-hemodynamic factors associated with left ventricular hypertrophy. 253 39

To determine whether acute effects of the angiotensin converting enzyme inhibitor lisinopril are maintained during long-term therapy, 19 patients were studied using right-sided heart catheterization before an initial randomized dose of lisinopril and again after 12 weeks of maintenance lisinopril therapy. During initial evaluation, lisinopril produced significant decreases in mean systemic arterial pressure, pulmonary artery wedge pressure, systemic vascular resistance, mean pulmonary arterial pressure, mean right atrial pressure and pulmonary vascular resistance, and concomitant increases in cardiac index and stroke volume index. After 12 weeks of therapy with lisinopril, the dosage of which was titrated to produce optimal relief of symptoms of congestive heart failure (CHF), repeat hemodynamic studies revealed persistent significant reductions in baseline systemic arterial pressure, pulmonary artery wedge pressure, mean pulmonary arterial pressure and systemic vascular resistance. However, the increases in cardiac index and stroke volume index were not statistically significant. To determine if further acute hemodynamic changes occur during long-term therapy, the patients were readministered a dose of lisinopril. This caused further decreases in systemic arterial pressure, mean pulmonary arterial pressure, pulmonary artery wedge pressure, systemic vascular resistance and mean right atrial pressure, and an increase in cardiac index. Lisinopril did not change stroke work index at either initial or rechallenge study. This study indicates that in patients with CHF treated with lisinopril, acute hemodynamic effects persist after 12 weeks of therapy, and acute hemodynamic response continues to occur upon drug readministration.
Am J Cardiol 1989 Mar 01
PMID:Hemodynamic effects of lisinopril after long-term administration in congestive heart failure. 253 66

Antibody interactions with the endothelial cell membrane glycoprotein angiotensin converting enzyme (Kininase II) in vivo exhibit features of aggregation and capping with resultant shedding similar to those events described in several in vitro isolated cell systems. Requirements for divalent ligand binding, deposition of complement and participation of cytoskeletal elements are demonstrated in vivo. Persistence of antigen in immune complexes with complement interaction appear to be necessary to induce an inflammatory response. Abrogation of this response occurs when circumstances permit antigenic modulation with removal of the immune complex from the endothelial surface.
J Mol Cell Cardiol 1989 Feb
PMID:Lung injury in rabbits induced by intravenous administration of heterologous polyclonal antibodies to angiotensin converting enzyme (kininase II). 254 26

In order to evaluate the action of an angiotensin converting enzyme inhibitor (Captopril) on the pulmonary hypoxic vasoconstriction, twenty one mongrel dogs were studied in two groups: group I with hypoxia, group II with normoxia. The dogs were anesthetized, intubated, and had their femoral vein and artery cannulated for blood-gas sampling and pressure records. They were mechanically ventilated with hypoxic gas mixtures (12.3% O2-87.7% N2)--group I and room air group II, at random. In both groups we measured, before and after administration of captopril 3 mg/kg intravenously, gas exchange and hemodynamic variables, as well as plasmatic levels of renin and angiotensin converting enzymes (ACE). Our results showed that the group I dogs decreased the systemic and pulmonary vascular resistances with small changes in pulmonary arterial pressures and no significant variations of pulmonary systemic resistances ratio. There were no significant variations of the same variables in the group II dogs. The gas exchange has not changed in either group of animals. In the group I dogs Captopril provoked systemic and pulmonary vasodilatation, with no gasometric and ventilation/perfusion ratio changes. In our experimental model we could not conclude that Captopril inhibited the hypoxic pulmonary vasoconstriction and/or that the angiotensin II had some action on the hypoxic pulmonary vasoconstriction mechanism, but there are some evidences favoring that hypothesis.
Arq Bras Cardiol 1989 Jun
PMID:[The role of angiotensin-converting enzyme inhibitor (captopril) on the mechanism of hypoxic pulmonary vasoconstriction. Experimental study in dogs]. 255 14

This review updates some recent advances of a new and exciting developments in basic and clinical cardiology: a) the role, in the congestive heart failure (CHF), of the neurohormonal systems (NHS) which act to maintain circulatory homeostatic equilibrium, and b) the therapeutic implications of such a role. Six NHS, acting in CHF, have presently been identified: three of them induce vasoconstriction and sodium retention (sympathetic nervous systems, renin-angiotensin-aldosterone system and arginine-vasopressine system); the remaining three offset or balance the former ones, acting, therefore as "counterregulators" (prostaglandins--PGE2 and PGI2--, dopaminergic system and atrial natriuretic factor). Each one of these NHS influences the "compensatory" mechanisms of heart failure, acting on the target-organs both by direct effects and by interaction with other NHS; consequently, in heart failure, all the NHS are stimulated with the respective increase in the plasma levels of their agents. In asymptomatic stages of ventricular dysfunction the stimulation of the vasodilator-and-natriuretic systems appears to be predominant and able to maintain circulatory equilibrium. However, as the heart dysfunction increases and becomes symptomatic, the vasoconstrictor and sodium-retaining forces appear to predominate; this phenomenon becomes increasingly apparent as the functional class becomes more advanced. The hyperstimulation of these last systems has an extremely important role in the pathophysiology and clinical manifestations of congestive heart failure, as well as in its prognosis. Therefore, the attempts to correct these neurohormonal imbalance in patients with heart failure has a sound rational basis, not only to improve the symptoms and the exercise capacity but also to increase the survival of these patients. At the present time, amongst the potential pharmacological interventions acting on NHS in CHF, the blockade of the SRA system with ACE-inhibitors is generally accepted as the most feasible, the safer and the most effective therapeutic tool. In fact, its application has broadened from an earlier use in severe CHF to other symptomatic stages of cardiac failure, including the milder forms. In addition, preliminary data strongly suggest its unique usefulness in asymptomatic phases of ventricular dysfunction. Looking back at the medical therapy of heart failure, it can be concluded that we are starting a new era. Throughout 200 years (since the introduction of digitalis) the therapeutic goal in CHF has been the improvement of symptoms. With the developments of the present decade, a new and exciting goal is being offered to these patients, called by Packer "the second frontier", that is, the prolongation of their lives.
Rev Port Cardiol 1989 Feb
PMID:[Neuro-hormonal mechanisms in heart insufficiency--from physiopathology to treatment]. 257 35

Digitalis therapy is usually ineffective in heart failure complicating myocardial infarction but may be of benefit in some selected patients with chronic heart failure. However, digitalis therapy in the long-term should be considered in conjunction with vasodilators or ACE inhibitors. This article reviews the practical and clinical aspects of vasodilator and digitalis therapy.
Cardiol Clin 1989 Feb
PMID:Digitalis and non-ACE inhibitor vasodilators in heart failure. 265 Aug 76

While antihypertensive therapy is considered to be an important clinical intervention in hypertensive patients, its effects on cardiac structure and function have not been intensely evaluated. In this study we tested the hypotheses that lowering blood pressure (BP) with the angiotensin I-converting enzyme inhibitor captopril, would: 1) normalize left ventricular mass and increase the cardiocyte mitochondria/myofibrils volume (Vmito/Vmyo) ratio; and 2) not compromise peak ventricular performance. We treated 16-week-old SHR and WKY with captopril (40-80 mg/kg) and hydrochlorothiazide (500 mg/l) via their drinking water. After six weeks of treatment peak cardiac performance was measured during rapid volume overload. Tissue samples from the left ventricular wall were analyzed by electron microscopy and stereology. Captopril lowered BP in SHR and WKY but had no affect on the left ventricular/body weight ratio. The only intracellular change in treated SHR was an increase in sarcoplasmic volume density. Treated WKY exhibited decreased midmyocardial mitochondrial volume density. At peak cardiac output, acceleration of flow and cardiac index were not affected by treatment. Stroke work at peak cardiac output was decreased in the treated groups due to a decrease in mean arterial pressure. In addition, captopril treatment resulted in a shift of the cardiac output (CO)-left ventricular end diastolic pressure (LVEDP) curves, such that LVEDP at peak cardiac output was approximately 50% less in the treated groups compared to their respective control groups. Although captopril was efficacious in lowering BP, it is suggested that lowering BP with this agent does not, at least within six weeks, lead to a reversal of hypertrophy or to a significant alteration in the volume densities of myofibrils and mitochondria. However, an important effect of this antihypertensive drug which may be of clinical significance, is that it leads to a leftward shift of the CO-LVEDP curve in both hypertensive and normotensive rats.
Basic Res Cardiol
PMID:Effects of captopril on left ventricular structure and function in SHR with established hypertension. 266 28

Short term angiotensin converting enzyme inhibition may induce a transient salt and water retention in patients with hypertension or heart failure. To verify the glomerular and tubular effects of short term converting enzyme inhibition, thirteen patients with mild to moderate essential hypertension (WHO I-II) were treated orally either with perindopril (4 mg o.d.) or captopril (25 mg b.i.d.) for one week. Both drugs reduced supine mean blood pressure significantly (p less than 0.01) (perindopril from 126 +/- 11 to 108 +/- 7 mmHg, mean +/- SD, and captopril from 132 +/- 12 to 121 +/- 16). Plasma volume (radio-iodinated albumin space) was unchanged while mean extracellular fluid volume (inulin space) increased although not significantly (from 5.05 +/- 1.32 l/sqm to 5.71 +/- 2.21 with perindopril and from 4.96 +/- 2.6 to 5.6 +/- 1.7 with captopril). Sodium clearance decreased (from 1.4 +/- 0.6 to 1.1 +/- 0.5 ml/min 1.73 sqm with perindopril, p less than 0.05, and from 0.97 +/- 0.44 to 0.88 +/- 0.51 with captopril, n.s.). In 9 patients (6 on captopril and 3 on perindopril) extra-cellular fluid volume increased simultaneously with reduction in glomerular filtration rate and in proximal tubule sodium re-absorption as well as an increase in distal tubule sodium reabsorption. In these patients the changes in proximal and distal tubule sodium reabsorption were significantly (p = 0.05) different from those of the patients with no extra-cellular fluid expansion.(ABSTRACT TRUNCATED AT 250 WORDS)
G Ital Cardiol 1989 May
PMID:[Volume of the extracellular liquid and renal function during short-term administration of angiotensin converting enzyme inhibitors in essential hypertension]. 267 Jun 57

Captopril, a potent inhibitor of angiotensin converting enzyme, was tested in patients with COPD (means forced expired volume in the first second--FEV1 = 0.73 l) and pulmonary hypertension (PAP = 41.3 mmHg). In the first phase of the experiment, patients underwent and incremental exercise test to the limit of tolerance. These were double blind, randomized, cross-over studies, where the patients received oral placebo (Pl) or captopril (Cp) 25 mg, on different days. In a second phase, the patients were submitted to hemodynamic and gasometric studies in the supine position, before placebo, the 60 min after and immediately after exercise (cycling-like leg movements). After 30 min of rest the same protocol was repeated with oral administration of 25 mg of captopril. In the metabolic evaluation (cycloergometry) captopril increased significantly exercise tolerance (means VO2-uptake at maximal exercise: CP = 0.81 vs Pl = 0.73 1/min), associated with a slower heart rate and higher O2-pulse at maximal exercise. In the hemodynamic study, when the effects of Cp and Pl were compared, the mean values of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) were similar at rest, but significantly lower during exercise, after captopril (means PAP Cp = 41.3 vs Pl = 51.2 mmHg; XPVR Cp = 278 vs Pl = 392 dyn. sec. cm5). There were similar systemic hemodynamic effects after Cp, but these were more intense in the pulmonary circulation (lower PVR/SVR ratio post-Cp in relation to post-Pl, during exercise). The cardiac index, systemic O2 transport and arterial and mixed venous blood gases were similar at rest and during exercise, with Pl or Cp.(ABSTRACT TRUNCATED AT 250 WORDS)
Arq Bras Cardiol 1989 Feb
PMID:[Effects of captopril on hemodynamics, gas exchange and exercise capacity in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease]. 268 2

Since the therapeutic advances prolong survival of many patients suffering from cardiovascular pathology--the prevalence of chronic heart failure (CHF) had just doubled, being a common entity in a world whose individuals present a great increase in longevity. These considerations justify the renewed interest in this particular syndrome. Concepts, pathophysiology and compensatory mechanisms are briefly summarized, putting emphasis on the advantage of pharmacologically interrupt the vicious loop of the compensatory mechanisms, that could play a deleterious role in the syndrome. Neurohormonal responses and the "pivotal" role of angiotensine II in CHF pathology are also discussed, emphasizing the benefits of angiotensin converting enzyme inhibitors (ACEI) when treating patients presenting heart failure. Questions addressed to its prescription at an early stage, (classes II and III of NYHA--to prevent the progressive exhaustion of the failing heart) are also considered. When approaching the preventive measures in a wide perspective, primary, secondary and tertiary types of preventive options are described. ACEI use for the least advanced clinical stages of CHF (class II and III) would represent a tertiary type of CHF prevention.
Rev Port Cardiol 1989 Mar
PMID:[Congestive heart insufficiency. Prophylactic aspects]. 269


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>