We tested the hypothesis that deletion of adenylyl cyclase type V (AC(V)) would be associated with decreased left ventricular (LV) contractile function and responsiveness to beta-adrenergic receptor (betaAR) stimulation. Absence of cardiac AC(V) expression was confirmed by RT-PCR and immunoblotting in AC(V)-deleted mice (AC(V) (-/-)). Compared to sibling mice with ...

Angiotensin-converting enzyme (ACE) inhibitors such as captopril, which block ANG II formation, are commonly used for treatment of hypertension. There is substantial evidence that the proximal tubule (PT) is a primary target site for captopril but the molecular mechanisms for its action in PT are not well defined. The aim ...

AIMS: It has been shown that both angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II type 1 receptor blockers (ARB) have renoprotective effects via mechanisms that are independent of blood pressure reduction. The aim of this study was to evaluate the intrarenal hemodynamic change with ARB by renal Doppler ultrasonography (RDU) ...

Angiotensin-converting enzyme (ACE) inhibitors are valuable agents for the treatment of hypertension, heart failure, and other cardiovascular and renal diseases. The cardioprotective effects of ACE inhibitors are mediated by blockade of both conversion of angiotensin (Ang) I to Ang II and kinin hydrolysis. Here, we report a novel mechanism that ...

Human epidemiological studies have shown that low birth weight is associated with hypertension in adulthood. Rodent models of intrauterine growth retardation (IUGR) support these findings because offspring from undernourished dams develop hypertension. Angiotensin-converting enzyme 2 (ACE2) is a newly described renin-angiotensin system (RAS) component that competes with ACE for angiotensin ...

OBJECTIVE: To determine the effects of angiotensin converting enzyme (ACE) inhibitors in hypertensive patients with aortic valve stenosis (AS). DESIGN: Observational, drug withdrawal, single blinded study, with randomisation of the order of tests. SETTING: Hypertension and asymptomatic AS. PATIENTS AND INTERVENTIONS: 20 patients (aged 73 (9) years, valve area 0.7 ...

BACKGROUND AND OBJECTIVES: Most of the pharmacokinetic (PK) parameters for enalapril and enalaprilat were established following determination of the drug and its metabolite, using angiotensin converting enzyme (ACE) inhibition assays. In these methods, enalapril has to be hydrolysed to enalaprilat first and then assayed. The purpose of this study was ...

BACKGROUND: We have shown that treatment of hypertension with ACE inhibitors (ACE-I) enhances relaxation to acetylcholine in human internal thoracic artery (ITA) above this in nonhypertensive patients receiving no ACE-I. Present study assesses the endothelium-dependent responses mediated by neither NO nor prostacyclin in human ITA. METHODS: We compared isolated ITA ...

Arrange for echocardiography or radionuclide angiography within 72 hours of a heart failure exacerbation. An ejection fraction >50% in the presence of signs and symptoms of heart failure makes the diagnosis of diastolic heart failure probable. To treat associated hypertension, use angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, ...

AIM: To evaluate the effect of ACE inhibitor moexipril if added to combination therapy in patient with poorly controlled hypertension. PATIENTS: Four hundred twenty patients with hypertension treated with monotherapy or two dug combination without an ACE inhibitor or AII antagonist and with blood pressure >/=140/90 mm Hg. DESIGN: Single-blind, ...

Some evidence suggests that long-term angiotensin-converting enzyme (ACE) inhibition may become less effective, thereby increasing angiotensin II levels, which could be inhibited by the addition of an angiotensin receptor blocker. We conducted a meta-analysis of randomized trials with searches of MEDLINE, EMBASE, and Cochrane databases. Overall, the combination of an ...

Remodeling of the arterial wall occurs mainly as a consequence of increased wall stress caused by hypertension. In this issue of the JCI, Azizi et al. report that in humans with a kallikrein gene polymorphism that lowers kallikrein activity, the brachial artery undergoes eutrophic inward remodeling in the absence of ...

Structural alterations of subcutaneous small resistance arteries are associated with a worse clinical prognosis in hypertension and noninsulin-dependent diabetes mellitus (NIDDM). However, no data are presently available about the effects of antihypertensive therapy on vascular structure in hypertensive patients with NIDDM. Therefore, we have investigated the effect of an angiotensin-converting ...

OBJECTIVE: To evaluate the evidence for valsartan in the treatment of heart failure and determine its need for formulary inclusion. DATA SOURCES: OVID and PubMed databases were searched (1983-June 2004) using the key words angiotensin-receptor blocker, heart failure, valsartan, Diovan, and angiotensin-converting enzyme inhibitor. Only English-language literature was selected. STUDY ...

Vasopeptidase inhibition is a novel treatment approach in cardiovascular disease such as hypertension and heart failure. Since the inhibition of the angiotensin-converting enzyme (ACE) turned out to represent a very successful principle in the treatment of hypertension in numerous large scale clinical studies, their results encouraged attempts to inhibit other ...

BACKGROUND: Ultrasonographic evidence of increased carotid intima-media thickness (IMT) is known to be associated with generalized atherosclerosis. Therapeutic blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme (ACE) inhibitors reportedly reduces carotid IMT in humans. However, there has been no head-to-head comparison of the effects of ACE inhibitor and angiotensin ...

Bradykinin and Lys-bradykinin are potent peptide mediators implicated in several physiopathological effects in mammals. They act through activation of G-protein-coupled constitutive B(2) or inducible kinin B(1) receptors linked to signaling pathways involving increased intracellular Ca(++) concentrations and/or release of mediators including arachidonic acid metabolites, NO and EDHF. In the cardiovascular ...

Recent immunosuppressive treatments for lupus nephritis have improved renal survival rate, however, there still exists lupus nephritis refractory to these treatments. Angiotensin receptor blockers (ARBs) are known not only to decrease blood pressure but also to have an independent renoprotecting effect by interrupting renin-angiotensin system. The aim of this study ...

INTRODUCTION: Individuals with tetraplegia rely on the renin-angiotensin system for orthostatic blood pressure control. OBJECTIVES: To determine the effect of partial angiotensin-converting enzyme (ACE) inhibition on heart rate (HR), active plasma renin (PR), and mean arterial blood pressure (MAP) during acute orthostasis in subjects with tetraplegia (n = 7) and ...

Chronic inhibition of nitric oxide (NO) synthesis is characterized by increased blood pressure accompanied with both cardiac hypertrophy as well as renal damage. We investigated whether the angiotensin-converting enzyme (ACE) inhibitor captopril can inhibit the cardiac hypertrophy and reverse the renal failure. We tested the influence of captopril on the ...

Hypertension is associated with cognitive impairment in older adults. The Hypertensive Old People in Edinburgh (HOPE) study reported improved scores in two psychometric tests in those subjects with the greatest fall in diastolic blood pressure during a 24-week randomised, double-blind trial of captopril versus bendrofluazide in 81 elderly hypertensive people ...

Angiotensin receptor blockers (ARBs) have a pharmacological role in the treatment of heart failure through their blockade of the effects of angiotensin II. ARBs, however, lack the potential benefits of inhibiting the breakdown of bradykinin that is seen with ACE-Is. Historically, the medical literature assessing ARBs in the treatment of ...

BACKGROUND: The renin-angiotensin-aldosterone system has a pivotal role in the short- and long-term regulation of blood pressure through its principal mediator, angiotensin II. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II-receptor blockers (ARBs) decrease the deleterious effects of angiotensin II on the vasculature and heart, but have different mechanisms of action. ...

Inhibition of the renin-angiotensin system with an angiotensin-converting enzyme inhibitor (ACEi) is an effective therapy in hypertension. Vasopeptidase inhibition was initially proposed with compounds inhibiting both angiotensin-converting enzyme and neutral endopeptidase (omapatrilat), but clinical trials revealed that reducing angiotensin II while blocking the degradation of vasodilatory peptides was not without ...

Angiotensin converting enzyme (ACE) inhibitors inhibit both the formation of angiotensin II and the catabolism of bradykinin (BK). They prevent not only hypertension but also cardiac hypertrophy and fibrosis. An increase in BK level stimulates the expression of nitric oxide (NO) synthase (NOS) and induces prostaglandins, both of which are ...

In this review, the basic mechanism of the parasympathetic nervous effect on the heart is discussed. This is expanded to clinical situations to clarify what can happen to patients after cholinesterase (ChE) inhibitor is administered and to avoid unnecessary adverse effects. The parasympathetic nervous system can affect heart as well ...

BACKGROUND AND AIM: An imbalance in the hemostatic system is a frequent finding in untreated essential hypertension (HT), and it has been shown that treatment with angiotensin converting entyme (ACE) inhibitors improves hemostatic function. In order to elucidate the role of genetic factors, we studied hemostasis in patients with untreated ...

BACKGROUND: Abdominal compartment syndrome (ACS) occurs when intra-abdominal pressure is abnormally high in association with organ dysfunction. It tends to have a poor outcome, even when treated promptly by abdominal decompression. METHODS: A search of the Medline database was performed to identify articles related to intra-abdominal hypertension and ACS. RESULTS: ...

Left ventricular hypertrophy (LVH) is frequently found at the initiation of dialysis therapy of diabetic and hypertensive patients, and is highly predictive of future cardiac morbidity and mortality. In patients with hypertension and LVH, both an angiotensin converting enzyme (ACE) inhibitor and an angiotensin type 1 receptor (AT1) antagonist regress ...

Recognition of the role of the renin-angiotensin-aldosterone system (RAAS) in initiating and maintaining hypertension prompted the development of drugs that disrupt the RAAS, notably the angiotensin-converting enzyme (ACE) inhibitors and, more recently, the angiotensin II receptor blockers (ARBs). This article focuses on the use of ARBs in hypertension management and ...

SLV306, a potent neutral endopeptidase (NEP) inhibitor with additional endothelin-converting enzyme (ECE)-inhibitory activity, in doses of 200, 400, and 800 mg reduced pulmonary and right atrial pressures, although there was not a clear dose response. Systemic blood pressure, heart rate, and cardiac output were unaffected. SLV306 increased plasma natriuretic peptides ...

BACKGROUND: Several publications in the past 2 years have demonstrated that combined angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor antagonist (AIIRA) are more effective in reducing blood pressure and proteinuria in patients with chronic renal disease than ACEI or AIIRA alone. This study compares the effect of increasing the ACEI ...

OBJECTIVES: To examine whether the favourable effects on endothelial function, vascular angiotensin converting enzyme (ACE) activity, cardiac remodelling, autonomic function, and QT intervals of spironolactone in combination with ACE inhibitor also occur in patients with New York Heart Association class I-II congestive heart failure (CHF) taking optimal treatment (including beta ...

Regardless of the underlying pathological mechanisms oxidative stress seems to be present in all forms of hypertension. Thus, we tested the hypothesis that chronic presence of high pressure itself elicits increased arterial O(2)(.-) production. Hypertension was induced in rats by abdominal aortic banding (Ab). Rats with Ab had elevated pressure ...

Authors inform about the group of 8 patients with abdominal compartment syndrome (ACS) occurred as a complication in large blunt injury of abdominal cavity. To the ACS diagnose, the measurement of intracystic pressure is used routinely, whose values correlate fully with values of intraabdominal pressure (IAP). In case of increasing ...

The present study compared short-term effects of the AT(1)-receptor antagonist, irbesartan with the angiotensin-converting enzyme (ACE) inhibitor, enalapril on systemic haemodynamics and cardiac remodelling in post-myocardia-infarcted (MI) rats. MI Sprague-Dawley rats were orally treated for 4 weeks with irbesartan (50 mg/kg/day) or enalapril (10 mg/kg/day). Then, cardiac and systemic haemodynamics ...

BACKGROUND: Several studies have shown antifibrotic effects of angiotensin converting enzyme (ACE) inhibitors as well as of angiotensin receptor 1 (AT1) antagonists, however, prospective trials with clinical end points comparing these effects do not exist. COL4A3-/- mice develop a non-hypertensive progressive renal fibrosis. We used this animal model to compare ...

BACKGROUND: Bradykinin is an endogenous vasodilator that may contribute to the systemic effects of angiotensin-converting enzyme (ACE) inhibitor therapy. Using B9340, a bradykinin receptor antagonist, we determined the contribution of bradykinin to the systemic hemodynamic effects of long-term ACE inhibition in patients with chronic heart failure. METHODS AND RESULTS: Fourteen ...

Based on the Medical Research Council study, Brown and Brown hypothesized in 1986 that angiotensin II could protect against strokes by causing vasoconstriction of the proximal cerebral arteries, thereby preventing Charcot-Bouchard aneurysms from rupturing. In light of this hypothesis, we evaluated the cerebroprotective effects of various drug classes in recent ...

Despite several decades of research into the renin-angiotensin system, new aspects of this endocrine system are elucidated every few years, expanding its role not only in hypertension but also in diabetes, oncology, and cardiology. In this review, we describe newly recognized physiologic actions of the angiotensin-converting enzyme (ACE). These include ...

Hypertension is the major controllable risk factor associated with cardiovascular disease (CVD) events such as myocardial infarction, stroke, heart failure, and end-stage diabetes. A 5 mm Hg decrease in blood pressure has been equated with approximately 16% decrease in CVD. In the U.S. alone current annual antihypertensive drug costs are ...

Clinical evidence in men with erectile dysfunction (ED) shows that the phosphodiesterase type 5 (PDE5) inhibitors sildenafil citrate, tadalafil, and vardenafil hydrochloride have favorable safety and efficacy profiles. However, as mild vasodilators, the PDE5 inhibitors are also associated with hemodynamic effects that may be clinically significant, especially when treating men ...

Omapatrilat inhibits neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE). We compared the effects of omapatrilat (40 mg/kg/day, p.o.) to fosinopril (40 mg/kg/day, p.o.) on flow-induced vascular remodeling in New Zealand genetically hypertensive (GH) rats. Both drugs equally reduced blood pressure (BP) initially, but systolic BP and pulse pressure were reduced ...

To clarify the mechanisms by which angiotensin-converting enzyme (ACE) inhibitors lower blood pressure or inhibit cardiac hypertrophy, we analyzed the correlations among tissue ACE activities, blood pressure and cardiac hypertrophy. In spontaneously hypertensive rats (SHR), blood pressure, heart weight and ACE activities in plasma and various tissues were measured 3, ...

Angiotensin-converting enzyme (ACE) generates angiotensin II and degrades bradykinin. This ectopeptidase acts as a marker in pathologic conditions, showing tissue and vascular damage. In order to evaluate serum and tissue ACE activity in bleomycin-associated lung damage, the authors studied morphological and enzymatic alterations as well as blood pressure in male ...

Angiotensin receptor blockers (ARBs) are highly effective antihypertensive agents with excellent safety profiles. ARBs have been shown to improve cardiovascular morbidity and mortality in hypertensive patients with heart failure or diabetic nephropathy. For this later class of patients, the American Diabetes Association recommends ARBs as the primary treatment option. The ...

INTRODUCTION: Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve endothelial function in Type 1 diabetes. However, the potential of ACE inhibitors (ACE-I) to enhance the haemodynamic effects of L-arginine (L-arg), the precursor of nitric oxide (NO), has not been evaluated. Furthermore, angiotensin receptor blockers (ARBs), another group of inhibitors ...

BACKGROUND: Vasopeptidase inhibition is a new antihypertensive approach combining inhibition of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), but severe oedema, mainly angio-oedema, has been reported. As ACE and NEP catalyse degradation of the permeability-increasing peptide bradykinin, and NEP also catalyses degradation of permeability-increasing peptides such as atrial natriuretic peptide, ...

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and the second Australian National Blood Pressure Study (ANBP2) came to different conclusions about which class of drug to try first for treating high blood pressure: a diuretic or an angiotensin-converting enzyme (ACE) inhibitor. But when examined closely, the ...

OBJECTIVES: This study sought to examine the alteration of local angiotensin converting enzyme (ACE) activity in the aortae, heart, kidney and lung as well as plasma during the development of hypertension in one-kidney, one-clip (1K1C) model, a non-renin-dependent model of renovascular hypertension. METHODS: Experiments were carried out 2, 4, 8 ...