Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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.
...
PMID:Overview of hemodynamic and non-hemodynamic factors associated with left ventricular hypertrophy. 253 39

Rats were killed after 6 weeks of continuous ingestion of the pneumotoxic alkaloid monocrotaline (2.2 mg/kg/day), the neutrophil elastase inhibitor SC39026 (60 mg/kg/day), or both. Pulmonary reactions were evaluated by light and electron microscopy. Lung endothelial function was monitored by angiotensin converting enzyme (ACE) activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Lung hydroxyproline content was measured as an index of interstitial fibrosis. Cardiac right ventricular hypertrophy was determined by the right ventricle to the left ventricle plus septum weight ratio (RV/LV + S). Rats receiving SC39026 alone did not differ significantly from untreated control animals with respect to any of the quantitative endpoints, although rarefaction of Type I pneumocytes was observed in the electron micrographs of these animals. Monocrotaline-treated rats, in contrast, developed a significant increase in RV/LV + S, and exhibited pulmonary edema, inflammation, fibrosis, and muscularization and occlusive mural thickening of the pulmonary small arteries and arterioles. These monocrotaline-induced structural changes were accompanied by decreased lung ACE and PLA activities, and increased PGI2 and TXA2 production, and by an increase in lung hydroxyproline content. Cotreatment with SC39026 ameliorated the monocrotaline-induced pulmonary vascular wall thickening and the cardiac right ventricular hypertrophy. These data suggest that inappropriate neutrophil elastase activity contributes to monocrotaline pulmonary vasculopathy and hypertension. On the other hand, cotreatment with SC39026 had no significant effect on the severity of the monocrotaline-induced lung inflammatory reaction, the pulmonary endothelial dysfunction, or the increase in lung hydroxyproline content.
...
PMID:Monocrotaline-induced cardiopulmonary injury in rats. Modification by the neutrophil elastase inhibitor SC39026. 254 80

Malignant hypertension developed in an 18-year-old man whose primary hypertension had been diagnosed by chance. Standing blood pressure was 290/170 mmHg. Tests of renal function revealed high blood urea nitrogen and creatinine levels and low levels of both effective renal plasma flow and the glomerular filtration rate. Plasma renin activity and levels of angiotensin II and aldosterone were greatly elevated. Severe concentric left ventricular hypertrophy was noted. The patient received standard antihypertensive treatment with furosemide, propranolol, nifedipine, and prazosin, but his blood pressure did not decrease and there was no improvement in the clinical or biochemical measures. The patient was then given 20 mg of enalapril daily for one year. The inhibition of angiotensin converting enzyme immediately reduced blood pressure. Angiotensin II and aldosterone levels became normal, kidney function and hemodynamics improved, and echocardiograms revealed that the left ventricular hypertrophy had regressed. The results confirm the pathogenetic role of angiotensin II in the development of the malignant phase of hypertension.
...
PMID:Treatment of malignant hypertension with an angiotensin converting enzyme inhibitor. 255 Jan 35

Established essential hypertension is characterised haemodynamically by a normal cardiac output and elevated total peripheral resistance. As hypertensive cardiovascular disease progresses, and the patient grows older, cardiac output falls and total peripheral resistance is further elevated. The activity of the renin-angiotensin-aldosterone (RAA) system declines throughout life and reaches its lowest levels in the elderly, unless there is congestive heart failure. In long-standing hypertension, target organ disease such as left ventricular hypertrophy, nephrosclerosis and cerebrovascular damage is commonly observed. Rational antihypertensive therapy should therefore aim to lower total peripheral resistance, spare cardiac output, and maintain or improve blood flow to target organs. ACE inhibitors lower arterial pressure by decreasing total peripheral resistance, they maintain or improve cardiac contractility, promote regression of left ventricular hypertrophy, and increase renal blood flow. Lisinopril is a novel ACE inhibitor that does not contain a sulphydryl group. It is not a prodrug and thus does not require bioactivation by the liver. Lisinopril has a long duration of action, allowing it to be used as a single daily dose in the treatment of hypertension. Preliminary studies from our laboratory indicate that lisinopril reduces cardiac output and preload to the left ventricle. Lisinopril also reduces left ventricular hypertrophy and lowers renal vascular resistance, thereby increasing renal blood flow. In patients with mild to moderate hypertension, lisinopril is more effective than hydrochlorothiazide in reducing both systolic and diastolic blood pressure, and is at least as effective as atenolol or metoprolol in reducing diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Lisinopril in the treatment of hypertension. 255 Jun 40

Lung injury induced in rats by the pyrrolizidine alkaloid monocrotaline is a well-documented model of pulmonary hypertension. To our knowledge, however, monocrotaline-induced cardiopulmonary injury has rarely been described and has never been quantitated in mice. In the present study, adult male mice received 2.4, 4.8, or 24.0 mg monocrotaline/kg body weight/day in the drinking water continuously for 6 weeks. These doses represent 1, 2, and 10 times the severely pneumotoxic regimen in rats. Pulmonary endothelial function was monitored by right lung angiotensin converting enzyme (ACE) activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Light and electron microscopy were performed on the left lungs. Cardiac right ventricular hypertrophy was evaluated by the right ventricle to left ventricle plus septum weight ratio (RV/LV + S). Monocrotaline-treated mice exhibited a dose-dependent decrease in lung ACE and PLA activities and an increase in PGI2 and TXA2 production, indicative of endothelial dysfunction. However, these responses were significant only after the highest monocrotaline dose. Light and electron microscopy revealed dose-dependent pulmonary inflammatory and exudative reactions. Unlike previous studies in rats, however, monocrotaline-treated mice developed relatively little lung fibrosis, cardiomegaly, or right ventricular hypertrophy, and no occlusive medial thickening of the pulmonary arteries, even at the highest dose level. These and previous data indicate that there are quantitative biochemical and qualitative morphological differences between mice and rats with respect to monocrotaline pneumotoxicity. Furthermore, in monocrotaline-treated mice (but not in rats) there appears to be a dissociation between lung endothelial dysfunction and inflammation on the one hand, and pulmonary hypertension and fibrosis on the other.
...
PMID:Monocrotaline pneumotoxicity in mice. 257 Apr 81

The interaction of salt with hypertension-induced left ventricular hypertrophy and its reversal by inhibition of angiotensin converting enzyme were studied in salt sensitive and salt resistant Dahl rats. Eight-week-old rats were fed either a low or high salt diet for three weeks. The colonies were then further divided and either treated with lisinopril or given no treatment for 11 weeks. Untreated salt sensitive rats had higher blood pressures than salt resistant animals. Left ventricular weight and wall thickness in both untreated salt sensitive groups was higher than in the resistant groups. Therapy lowered blood pressures in all groups but those of the high salt group remained higher than the low salt group. Reduction of left ventricular weight and wall thickness took place in either strain only when salt intake was low. Right ventricular and atrial weights were largely unaffected either by salt intake or drug therapy. Plasma renin activity increased and aldosterone levels decreased with lisinopril therapy in all groups except the salt sensitive, high salt group where both remained unchanged at low levels. Lisinopril was effective in reducing blood pressure and left ventricular hypertrophy, but both effects were severely impaired by high salt intake. The major determinant of left ventricular hypertrophy appeared to be afterload, as shown by a good correlation between left ventricular mass and systolic blood pressure, but there was some indication of a possible independent hypertrophic action of salt.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Correlation of left ventricular hypertrophy and its regression by lisinopril with salt-induced hypertension. 284 21

The interactions of blood pressure, salt intake and angiotensin converting enzyme (ACE) inhibition were investigated in the Dahl salt-sensitive (DS) and salt-resistant (DR) strains of rats. Eight-week-old DS and DR (40 of each) were separately randomized to receive a low- (0.4% NaCl) or a high- (8% NaCl) salt diet for 3 weeks. Thereafter the rats were further separated randomly to receive the ACE inhibitor lisinopril (3-8 mg/kg per day) or no drug treatment for 11 weeks. In untreated DS rats blood pressure rose, paralleled by a higher left ventricular mass (ratio left ventricular weight/body weight) irrespective of salt intake. Lisinopril lowered blood pressure to normotensive levels in all groups except DS rats on a high-salt diet, despite doses of up to 100 mg/kg per day, although there was a significant fall in blood pressure. Lisinopril reduced left ventricular mass significantly on the low- but not on the high-salt diet. Plasma renin activity increased on lisinopril treatment in all groups except DS rats on the high-salt diet. Regression of an increased left ventricular mass by ACE inhibition seemed to be impaired by a high salt intake, even when blood pressure was lowered. Therefore, although for regression of left ventricular hypertrophy, reduction of afterload was the leading factor, this might be adversely affected by a high salt intake.
...
PMID:Modulation of left ventricular hypertrophy by dietary salt and inhibition of angiotensin converting enzyme. 285 24

The conventional "stepped-care" approach to the treatment of hypertension deserves revision. Rational therapy considers a variety of factors to obtain maximum efficacy, safety, tolerability, compliance, and neutralization of neural tone for the prevention of sudden death. The patient's age, gender, race, behavior profile, hemodynamic and neurohumoral status (plasma renin activity, norepinephrine/epinephrine ratio), and quality of life will help determine the choice of antihypertensive agent. Concomitant risk factors (smoking, obesity, diabetes, hypercholesterolemia), the presence of sequelae (left ventricular hypertrophy and/or failure, renal failure), and the existence of other disorders (mitral valve prolapse, depression, anxiety) must also be considered when initiating treatment. In addition, the cost of ancillary expenses (laboratory tests, hospitalizations, and emergency room visits) must be weighed against the potential benefits of therapy. Beta blockers are effective, well tolerated, and versatile for the treatment of concomitant cardiovascular disorders and as behavior modifiers. Calcium channel blockers and angiotensin converting enzyme inhibitors also show promise and merit consideration as therapy for specific groups of hypertensive patients.
...
PMID:The 1980s: a patient-specific therapeutic approach in hypertension. 288 36

Pharmacotherapeutical means of reversing cardiac hypertrophy (prazosin, clonidine and nifedipine) were analysed in concentrically, as well as eccentrically, hypertrophied left ventricles. Regression of cardiac hypertrophy, i.e. a therapeutic intervention on a critical precursor of hypertensive congestive heart failure, can be obtained by various antihypertensive agents. Prazosin, calcium channel blockers, clonidine and angiotensin converting enzyme inhibitors as well as a combined treatment regimen using alpha-receptor blockers together with diuretics and vasodilators can all induce regression of hypertrophy associated with an improvement in left ventricular function. Moreover, an improved coronary reserve may reduce the ischaemic risk of the hypertrophied myocardium. However, not all antihypertensive drugs seem equally effective in bringing about coronary regression of left ventricular hypertrophy (LVH). No regression or little regression has been found with diuretic monotherapy despite a satisfactory reduction in blood pressure. On the other hand, a trend towards a regression has been observed in patients in whom treatment with clonidine significantly reduced catecholamines.
...
PMID:The influence of sympathetic nervous activity on regression of cardiac hypertrophy. 293 89

Arterial hypertension is by definition a haemodynamic disorder. At least 3 different subsets of cardiovascular pathophysiological features can be identified in so-called essential hypertension: The young lean patient characterised by an elevated cardiac output and renal blood flow, elevated plasma renin activity and circulating catecholamine levels, as well as symptoms and signs of hyperadrenergic hypertension. The elderly patient characterised by a low cardiac output often with left ventricular hypertrophy, elevated total peripheral resistance, nephrosclerosis, and symptoms and signs of target organ disease. The obese patient (and to a lesser degree the black patient) characterised by expanded fluid volume state, elevated cardiac output, a normal to low total peripheral resistance, and symptoms and signs of volume overload. To initiate antihypertensive therapy, the drug of choice in the young patient is a beta-adrenergic receptor blocker; in the elderly it is a haemodynamic vasodilator (anti-adrenergic drug, slow channel calcium blocker, or converting enzyme (ACE) inhibitor), and in black or obese patients it remains a thiazide diuretic. Enalapril, a new ACE inhibitor is indicated as a first-step agent in the great majority of hypertensive patients in whom the elevated arterial pressure should be reduced by a decrease in total peripheral resistance, without compromising systemic or regional blood flow. In contrast to other antihypertensive agents, enalapril will lower preload and afterload to the left ventricle while improving systemic and regional flow in elderly patients with latent or manifest congestive heart failure.
...
PMID:Cardiovascular pathophysiology of essential hypertension: a clue to therapy. 299 85


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

---