Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2.

Background: Angiotensin converting enzyme (ACE) 2 is a recently identified homologue of ACE that may counterregulate the actions of angiotensin (Ang) II by facilitating its breakdown to Ang 1-7. The renin-angiotensin system (RAS) has been implicated in the pathogenesis of cirrhosis but the role of ACE2 in liver disease is not known.

Aims: This study examined the effects of liver injury on ACE2 expression and activity in experimental hepatic fibrosis and human cirrhosis, and the effects of Ang 1-7 on vascular tone in cirrhotic rat aorta.

Immunolocalization of ACE2 and AT2 receptors in rabbit atherosclerotic plaques.

Evidence suggests that angiotensin type 2 receptor (AT2R) and angiotensin-converting enzyme 2 (ACE2) play a protective role in atherogenesis. These factors have not been identified in rabbit atherosclerotic plaques. Our goal was to localize ACE2 and AT2R in rabbit atherosclerotic tissues, and determine which cell types express these factors.

Connective tissue growth factor and cardiac fibrosis after myocardial infarction.

The temporal and spatial expression of transforming growth factor (TGF)-beta(1) and connective tissue growth factor (CTGF) was assessed in the left ventricle of a myocardial infarction (MI) model of injury with and without angiotensin-converting enzyme (ACE) inhibition. Coronary artery ligated rats were killed 1, 3, 7, 28, and 180 days after MI. TGF-beta(1), CTGF, and procollagen alpha1(I) mRNA were localized by in situ hybridization, and TGF-beta(1) and CTGF protein levels by immunohistochemistry.

Glomerular permeability defect in hypertension is dependent on renin angiotensin system activation.

Background: The aim of the present study was to compare glomerular permeability alterations associated with experimental hypertension models known to have different effects on the circulating renin-angiotensin system (RAS).

Methods: Five groups, 10 animals each, were studied. One group served as a nonhypertensive control.

Lateral vs medial mitral annular tissue Doppler in the echocardiographic assessment of diastolic function and filling pressures: which should we use?

Tissue Doppler echocardiography (TDE) is used in the assessment of diastolic function, however, it is unclear whether the medial (E' med) or lateral (E' lat) annulus should be used. Our aim was to compare the diagnostic utility of E' med and E' lat. In 232 subjects left ventricular (LV) systolic and diastolic function was assessed via transthoracic echocardiography with TDE measurements obtained from both annuli.

Myocardial infarction increases ACE2 expression in rat and humans.

Aims: Angiotensin converting enzyme (ACE) 2 catalyses the cleavage of angiotensin (Ang) I to Ang 1-9 and of Ang II to Ang 1-7. ACE2 deficiency impairs cardiac contractility and upregulates hypoxia-induced genes, suggesting a link with myocardial ischaemia. We studied the expression of ACE2 after myocardial infarction (MI) in the rat as well as in human failing hearts.

Thiazolidinediones and congestive heart failure--exacerbation or new onset of left ventricular dysfunction?

Background: Patients with diabetes mellitus have a high incidence of coronary heart disease and congestive heart failure (CHF). Thiazolidinediones (TZD) are a new class of pharmacological agents for the treatment of Type 2 diabetes mellitus, which have many beneficial cardiovascular effects. Peripheral oedema and weight gain have been reported in 4.

Randomized trial of a statewide home visiting program to prevent child abuse: impact in reducing parental risk factors.

Objectives: To assess the impact of a home visiting program in reducing malleable parental risk factors for child abuse in families of newborns identified, through population-based screening, as at-risk of child abuse.

Methods: This randomized trial focused on Healthy Start Program (HSP) sites operated by three community-based organizations on Oahu, HI, USA. From 11/94 to 12/95, 643 families were enrolled and randomly assigned to intervention and control groups.

Randomized trial of a statewide home visiting program: impact in preventing child abuse and neglect.

Objectives: To assess the impact of home visiting in preventing child abuse and neglect in the first 3 years of life in families identified as at-risk of child abuse through population-based screening at the child's birth.

Methods: This experimental study focused on Hawaii Healthy Start Program (HSP) sites operated by three community-based agencies. From 11/94 to 12/95, 643 families were enrolled and randomly assigned to intervention and control groups.

ACE2, a new regulator of the renin-angiotensin system.

Angiotensin-converting enzyme (ACE) is a zinc metalloproteinase and a key regulator of the renin-angiotensin system (RAS). ACE2 is a newly described enzyme identified in rodents and humans with a more restricted distribution than ACE, and is found mainly in heart and kidney. ACE2 cleaves a single residue from angiotensin I (Ang I) to generate Ang 1-9, and degrades Ang II, the main effector of the RAS, to the vasodilator Ang 1-7.

Cardiorenal protective effects of vasopeptidase inhibition with omapatrilat in hypertensive transgenic (mREN-2)27 rats.

Vasopeptidase inhibitors simultaneously inhibit both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). The aim of this study was to determine the cardiorenal effects of the vasopeptidase inhibitor omapatrilat in the transgenic m(Ren-2)27 rat which exhibits fulminant hypertension and severe organ pathology. At 6 weeks of age, male Ren-2 rats were randomized to receive no treatment (N = 10), the ACE inhibitor fosinopril 10 mg/kg/day (N = 10), or omapatrilat 10 mg/kg/day (N = 10) or 40 mg/kg/day (N = 10) by daily gavage for 24 weeks.

Evaluating a statewide home visiting program to prevent child abuse in at-risk families of newborns: fathers' participation and outcomes.

This study sought to describe fathers' participation in a statewide home-visiting program to prevent child abuse and to assess program impact on their parenting. This randomized trial followed 643 at-risk families for 3 years. Data were collected through program record review, staff surveys, and annual maternal interviews.

Diabetes mellitus: a cardiovascular disease.

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with diabetes mellitus (DM). The pathophysiology of CVD in diabetes involves traditional and novel cardiac risk factors, including hypertension, dyslipidemia, smoking, genetic factors, hyperglycemia, insulin resistance/hyperinsulinemia, metabolic abnormalities, oxidative/glycoxidative stress, inflammation, endothelial dysfunction, a procoagulant state and myocardial fibrosis. Specific vascular, myopathic and neuropathic alterations have been suggested to be responsible for the excessive cardiovascular morbidity and mortality in diabetes.

Renoprotective effects of vasopeptidase inhibition in an experimental model of diabetic nephropathy.

Aims: Although ACE inhibitors slow progression of diabetic renal disease, the mortality and morbidity is still high. As other hormonal factors are involved, inhibition of vasopeptidases could further reduce progression. We studied dual inhibition of angiotensin converting enzyme and neutral endopeptidase in a model of progressive diabetic renal injury.

Upregulation of cardiac insulin-like growth factor-I receptor by ACE inhibition after myocardial infarction: potential role in remodeling.

This study evaluated the effects of angiotensin-converting enzyme (ACE) inhibition after myocardial infarction (MI) on cardiac remodeling and gene expression and localization of components (ligands, receptors, and binding proteins) of the cardiac insulin-like growth factor (IGF) system. After ligation of the coronary artery, rats were randomized to vehicle or ACE inhibitor (Captopril, 50 mg/kg/day) for 4 weeks. Blood pressure, cardiac remodeling, and components of the IGF system were localized in the heart using in situ hybridization (ISH) and immunohistochemistry (IHC).

Differential tissue and enzyme inhibitory effects of the vasopeptidase inhibitor omapatrilat in the rat.

Vasopeptidase inhibitors simultaneously inhibit angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). The present study characterized the tissue distributions of ACE and NEP, and assessed the effects of the vasopeptidase inhibitor omapatrilat on ACE and NEP in rat tissues. In vivo ACE and NEP inhibition was studied by in vitro autoradiography and using the ACE inhibitor radioligand (125)I-MK351A and the NEP inhibitor radioligand (125)I-RB104 in rats that received oral omapatrilat (40 mg x day(-1) x kg(-1)) for 3 days.

Vasopressin receptor expression in the placenta.

The arginine vasopressin (AVP) type 1a receptor (V1a) is well known to mediate vasoconstriction. In pregnancy, blood flow in the placenta is crucial for sustaining normal growth and development of the fetus. This is the first AVP receptor study in the placenta and fetal membranes.

Cardiovascular hypertrophy in diabetic spontaneously hypertensive rats: optimizing blockade of the renin-angiotensin system.

The aim of the present study was to compare the antihypertrophic effects of blockade of the renin-angiotensin system (RAS), vasopeptidase inhibition and calcium channel antagonism on cardiac and vascular hypertrophy in diabetic spontaneously hypertensive rats (SHR). SHR with streptozotocin-induced diabetes were treated with one of the following therapies for 32 weeks: the angiotensin-converting enzyme (ACE) inhibitor captopril (100 mg/kg); the angiotensin AT(1) receptor antagonist valsartan (30 mg/kg); a combination of captopril with valsartan; the vasopeptidase inhibitor mixanpril (100 mg/kg); or the calcium channel antagonist amlodipine (6 mg/kg). Systolic blood pressure and cardiac and mesenteric artery hypertrophy were assessed.

Characterization of renal angiotensin-converting enzyme 2 in diabetic nephropathy.

ACE2, initially cloned from a human heart, is a recently described homologue of angiotensin-converting enzyme (ACE) but contains only a single enzymatic site that catalyzes the cleavage of angiotensin I to angiotensin 1-9 [Ang(1-9)] and is not inhibited by classic ACE inhibitors. It also converts angiotensin II to Ang(1-7). Although the role of ACE2 in the regulation of the renin-angiotensin system is not known, the renin-angiotensin system has been implicated in the pathogenesis of diabetic complications and in particular in diabetic nephropathy.

A breaker of advanced glycation end products attenuates diabetes-induced myocardial structural changes.

The formation of advanced glycation end products (AGEs) on extracellular matrix components leads to accelerated increases in collagen cross linking that contributes to myocardial stiffness in diabetes. This study determined the effect of the crosslink breaker, ALT-711 on diabetes-induced cardiac disease. Streptozotocin diabetes was induced in Sprague-Dawley rats for 32 weeks.

Inhibition of peptidases in the control of blood pressure.

The natriuretic peptide and renin-angiotensin systems are physiological counterparts with opposite roles in the regulation of electrolyte balance and blood pressure. In both systems, membrane-bound, zinc-dependent peptidases play an important role in the inactivation or activation of the system. Angiotensin-converting enzyme (ACE) converts angiotensin I into angiotensin II, and neutral endopeptidase (NEP) degrades the natriuretic peptides.

The effect of volunteer home visitation for adolescent mothers on parenting and mental health outcomes: a randomized trial.

Background: Children of adolescent mothers may suffer because of parenting inadequacies. The use of volunteer home visitors to enhance parenting skills has not been well studied.

Objective: To evaluate the effect of a volunteer model home visitation program on adolescent parenting outcomes.

Up-regulation of components of the renin-angiotensin system in the bile duct-ligated rat liver.

Background & Aims: Angiotensin II (ANG II) has profibrotic actions in the heart and kidney, whereas blockade of the renin angiotensin system (RAS) attenuates injury. This study examines whether the RAS is present in the liver and examines its regulation in the bile duct-ligation model of hepatic fibrogenesis.

Methods: Sham-operated and bile duct-ligated (BDL) Sprague-Dawley rats were studied.