Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro studies have demonstrated that angiotensin II (ANG II) induces adipocyte hyperplasia and hypertrophy. The aim of the present study was to determine the effect of angiotensin-converting enzyme inhibition on body weight, adiposity and blood pressure in Sprague-Dawley rats. From birth half of the animals (n=15) were given water to drink, while the remainder were administered perindopril in their drinking water (2 mg/kg/day). Food intake, water intake and body weight were measured weekly. Blood pressure was measured by tail cuff plethysmography at 11-weeks. Body fat content and distribution were assessed using dual energy X-ray absorptiometry and Magnetic Resonance Imaging at 12 weeks. Animals administered with perindopril had a body fat proportion that was half that of controls. This was consistent with, but disproportionately greater than the observed differences in food intake and body weight. Perindopril treatment completely removed hypertension. We conclude that the chronic inhibition of ANG II synthesis from birth specifically reduces the development of adiposity in the rat.
 ...
PMID:Angiotensin converting enzyme inhibition from birth reduces body weight and body fat in Sprague-Dawley rats. 1819 66

Stroke is one of the leading causes of disability and death worldwide and is a more common cause of cardiovascular morbidity and mortality than myocardial infarction among patients with hypertension. Identifying and modifying key risk factors is crucial to reduce morbidity and mortality from stroke. Hypertension is the most important modifiable risk factor for ischemic stroke, and antihypertensive treatment is of paramount importance to reduce the incidence of stroke mortality and morbidity. Perindopril is a third-generation long acting, once-daily lipophilic angiotensin-converting enzyme inhibitor with high tissue angiotensin-converting enzyme affinity, lowering angiotensin II and potentiating bradykinin. Its efficacy, safety and tolerability are well established in the treatment of hypertension and heart failure. The purpose of this article is to review the evidence from clinical trials as well as from recent patents that has been gathered in regard to perindopril, demonstrating not only its efficacy in reducing blood pressure, but also to other cardiovascular protective properties that act in addition to the obvious blood-pressure-lowering effect in the prevention of stroke in patients with essential hypertension, with particular attention paid to the results from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS).
 ...
PMID:Role of perindopril in the prevention of stroke. 1822 Oct 93

Dementia is a common and serious health problem that affects 33 million persons globally. With the increase in life expectancy, the prevalence of dementia is expected to reach 81.1 million persons by 2040. Dementia impairs quality of life and is associated with profound disease burden, morbidity, and mortality in both patients and caregivers. Therefore, identifying measures to prevent dementia is a research priority. Midlife hypertension has increased the risk of dementia in large prospective cohort studies. Researchers have investigated the blood pressure-lowering effects of antihypertensive drugs on the incidence of dementia. Although prospective cohort studies have shown that use of antihypertensive drugs was associated with a reduced rate of cognitive impairment and dementia, these studies were not placebo controlled. Four randomized, placebo-controlled studies-the Systolic Hypertension in Europe (Syst-Eur) study, Study on Cognition and Prognosis in the Elderly (SCOPE), Systolic Hypertension in the Elderly Program (SHEP), and Perindopril Protection Against Recurrent Stroke Study (PROGRESS)-investigated the effects of antihypertensive agents on the incidence of dementia. The Syst-Eur study found that active treatment with nitrendipine, enalapril, and/or hydrochlorothiazide reduced the rate of dementia by 50% compared with placebo (p=0.05). The PROGRESS study showed that active treatment with perindopril and indapamide was associated with reduced cognitive decline compared with placebo (risk ratio 19%, p=0.01). In contrast, the SCOPE study (candesartan or hydrochlorothiazide vs placebo) and the SHEP trial (chlorthalidone, atenolol, or reserpine vs placebo) found no significant difference between the active treatment and placebo groups on the incidence of dementia. Some researchers have suggested that certain antihypertensive drug classes, such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, diuretics, and calcium channel blockers, may offer benefit in reducing dementia risk in addition to their blood pressure-lowering effect. Further prospective randomized studies comparing different antihypertensive classes are needed to provide more evidence regarding the effects of antihypertensive drugs on dementia risk and to determine whether certain antihypertensive classes provide greater benefits than others.
 ...
PMID:Effects of antihypertensive drug treatment on the risk of dementia and cognitive impairment. 1829 16

The role of angiotensin-converting enzyme (ACE) inhibitors in diabetic patients with preserved ventricular function is uncertain. Tissue ACE inhibitors have been defined by increased lipophilicity and structural characteristics that result in greater tissue-specific ACE binding when compared with plasma ACE inhibitors. A Bayesian meta-analysis of randomized trials was conducted to evaluate tissue ACE inhibitors in prevention of cardiovascular disease among patients with diabetes mellitus and preserved left ventricular function. Four trials were selected that evaluated 2 different ACE inhibitors and included 10,328 patients (43,517 patient-years). The Perindopril Substudy in Coronary Artery Disease and Diabetes (PERSUADE) and the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) compared the effects of perindopril vs a placebo, and the Heart Outcomes Prevention Evaluation (HOPE) and the Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) study investigated the impact of ramipril vs a placebo. Bayesian meta-analysis of sequential trials and sensitivity analysis of therapeutic response were subsequently computed. Bayesian meta-analysis determined reduced risk of cardiovascular mortality (PB=.991), myocardial infarction (PB=.999), and the need for invasive coronary revascularization (PB=.995) when compared with placebo. Total mortality was also decreased (PB=.967), while the risk of stroke (PB=.907) and hospitalization for heart failure (PB=.923) were impacted. Bayesian meta-analysis of randomized trials suggests that tissue ACE inhibitors decrease the probability that diabetic patients with preserved left ventricular function will experience myocardial infarctions and cardiovascular death and reduce overall mortality.
 ...
PMID:Bayesian meta-analysis of tissue angiotensin-converting enzyme inhibitors for reduction of adverse cardiovascular events in patients with diabetes mellitus and preserved left ventricular function. 1832 70

We analyzed the effect of hypertension on postischemic vasculogenesis. Ischemia was induced by right femoral artery ligature in Wistar Kyoto rats (WKY) or spontaneously hypertensive rats (SHR) treated with or without angiotensin-converting enzyme inhibitor (Perindopril, 0.76 mg/kg/d) and angiotensin type 1 receptor blocker (losartan, 30 mg/kg/d). Basal postischemic neovascularization was reduced in SHR compared to WKY (P<0.05, n=8). Treatment with ACE inhibitor or angiotensin type 1 receptor blocker decreased blood pressure levels by 1.4- and 1.3-fold (P<0.001), respectively and restored vessel growth in SHR to WKY levels. Interestingly, 14 days after bone-marrow mononuclear cell (BM-MNC) transfusion, angiographic scores, capillary density, and foot perfusion were decreased by 1.4-, 1.5-, and 1.2-fold, respectively in SHR transfused with BM-MNCs isolated from SHR compared to those receiving BM-MNCs of WKY (P<0.05, n=6). Alteration in BM-MNCs proangiogenic potential was likely related to the reduction in their ability to mobilize into peripheral circulation, as revealed by the 2.9-fold decrease in number of circulating CD34+/CD117+ cells (P<0.001) and to differentiate into cells with endothelial phenotype, as revealed by the 2.1-fold reduction in percentages of DilLDL/BS-1 lectin positive cells (P<0.001). In addition, reactive oxygen species (ROS) levels were increased by 2.2-fold in SHR BM-MNCs compared to WKY BM-MNCs (P<0.01), as assessed by L-012 luminescence. Cotreatment with ACE inhibitor, angiotensin type 1 receptor blocker, or antioxidants (NAC 3 mmol/L, Apocynin 200 micromol/L) reduced ROS levels, improved the number of DilLDL/BS-1 lectin-positive cells by around 1.5-fold, and restored BM-MNCs proangiogenic effects in ischemic hindlimb. In conclusion, alteration in progenitor cell proangiogenic function may participate to the hypertension-induced impairment in postischemic revascularization.
Hypertension 2008 Jun
PMID:Hypertension impairs postnatal vasculogenesis: role of antihypertensive agents. 1842 93

The angiotensin-converting enzyme (ACE) inhibitor perindopril (Coversyl) is a long-acting lipophilic drug with a high-tissue affinity for the ACE. ACE inhibition by perindopril has two main effects: it inhibits the angiotensin II formation and potentiates bradykinin. Perindopril is one of the ACE inhibitors that has been extensively studied in randomized clinical trials within various patient populations. The clinical efficacy has been demonstrated in patients with hypertension, diabetes mellitus, cerebrovascular disease, stable coronary artery disease (CAD) and heart failure. Perindopril has a positive safety and tolerability profile. Therefore, perindopril, as an ACE inhibitor, has an established place in the major clinical treatment guidelines. This article discusses several studies that have shown that an antihypertensive treatment with perindopril reduces and prevents cardiovascular events in a large range of patients with established vascular disease. The observed cardioprotective benefits of perindopril were independent of blood pressure. The outcome of these and other trials support the concept of specific cardioprotective properties of ACE inhibition by perindopril in addition to the blood pressure-lowering effects, such as anti-atherosclerotic, anti-inflammatory and antithrombotic properties. In addition, the observed consistency of the treatment benefit across subgroups indicates that the absolute benefits conferred by treatment are mainly established by each patient's future risk of vascular complications, rather than their initial blood pressure level or other risk factors. This article describes these issues according to the main studies with perindopril or perindopril-based regimens, concluding that the blood pressure-dependent and -independent cardioprotective effects extend to all patients with vascular disease. This concept supports the provision of ACE inhibitor-based treatment, not on the basis of arbitrary cut-off points for blood pressure but rather on assessment of vascular risk, which is raised in patients with stable CAD, diabetes and stroke.
 ...
PMID:Angiotensin-converting enzyme inhibition by perindopril in the treatment of cardiovascular disease. 1937 59

Perindopril, a prodrug ester of perindoprilat, is an angiotensin-converting enzyme inhibitor that lowers angiotensin II and potentiates bradykinin. This agent has proven efficacy in a wide range of cardiovascular diseases. Its efficacy, safety and tolerability are well established in the treatment of hypertension. Beyond pharmacodynamic effects shown in lowering blood pressure, perindopril was also involved in the improvement of endothelial function and the normalization of vascular and cardiac structure and function. Large morbidity-mortality trials, such as the European Trial on Reduction of Cardiac Events with Perindopril in Patients with Stable Coronary Artery Disease (EUROPA), Perindopril Protection Against Recurrent Stroke Study (PROGRESS) and Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA), have shown that treatment with perindopril reduces and prevents cardiovascular disease in a large range of patients with vascular diseases (including stable coronary disease), whether or not they are hypertensive.
 ...
PMID:Perindopril: beyond lowering blood pressure. 1980 27

Angiotensin II is a potent growth factor involved in arterial wall homeostasis. In resistance arteries, chronic increases in blood flow induce a rise in diameter associated with arterial wall hypertrophy. Nevertheless, the role of angiotensin II in this remodeling is unknown. We investigated the effect of blocking angiotensin II production or receptor activation on flow-induced remodeling of mesenteric resistance arteries. Arteries were ligated in vivo to generate high-flow arteries compared with normal flow (control) vessels located at a distance. Arteries were isolated after 1 week for in vitro analysis. Arterial diameter, media surface, endothelial NO synthase expression, superoxide production, and extracellular signal-regulated kinase 1/2 phosphorylation were higher in high-flow than in control arteries. Angiotensin-converting enzyme inhibition (perindopril) and angiotensin II type 1 receptor blockade (candesartan) prevented arterial wall hypertrophy without affecting diameter enlargement. The nonselective vasodilator hydralazine had no effect on remodeling. Although perindopril and candesartan increased endothelial NO synthase expression in high-flow arteries, hypertrophy remained in rats treated with N(G)-nitro-l-arginine methyl ester and mice lacking endothelial NO synthase. Perindopril and candesartan reduced oxidative stress in high-flow arteries, but superoxide scavenging did not prevent hypertrophy. Both Tempol and the absence of endothelial NO synthase prevented the rise in diameter in high-flow vessels. Extracellular signal-regulated kinase 1/2 activation in high-flow arteries was prevented by perindopril and candesartan and not by hydralazine. Extracellular signal-regulated kinase 1/2 inhibition in vivo (U0126) prevented hypertrophy in high-flow arteries. Thus, a chronic rise in blood flow in resistance arteries induces a diameter enlargement involving NO and superoxide, whereas hypertrophy was associated with extracellular signal-regulated kinase 1/2 activation by angiotensin II.
Hypertension 2010 Jan
PMID:Role of angiotensin II in the remodeling induced by a chronic increase in flow in rat mesenteric resistance arteries. 1994 89

There is considerable uncertainty regarding the efficacy of blood pressure-lowering therapy in reducing cardiovascular risk in obese people. In this report we examine the effects of blood pressure lowering according to baseline body mass index (kilograms per meter squared) in the Perindopril Protection Against Recurrent Stroke Study. A total of 6105 participants with cerebrovascular disease were randomized to perindopril-based blood pressure-lowering therapy or placebo. The overall mean difference in systolic/diastolic blood pressure between participants assigned active therapy or placebo was 9/4 mm Hg (SE: 0.5/0.3 mm Hg), with no difference by body mass index quarters (<23.1, 23.1 to 25.3, 25.4 to 27.8, and > or = 27.9 kg/m(2)). A consistent treatment benefit was demonstrated for protection against major vascular events across quarters with the following hazard ratios (95% CIs): 0.80 (0.62 to 1.02), 0.78 (0.61 to 1.01), 0.67 (0.53 to 0.86), 0.69 (0.54 to 0.88), and 0.74 (0.66 to 0.84; P for heterogeneity=0.16). Similar results were apparent for stroke and stroke subtypes (all P for heterogeneity > or = 0.07) or with the standard definitions of overweight and obesity (<25, 25 to 29, and > or = 30 kg/m(2); all P for heterogeneity > or = 0.28). The absolute effects of treatment were, however, more than twice that in the highest compared with the lowest body mass index quartile. Across increasing quarters of body mass index over 5 years, active therapy prevented 1 major vascular event among every 28, 23, 13, and 13 patients treated. In conclusion, blood pressure-lowering therapy produced comparable risk reductions in vascular disease across the whole range of body mass indices in participants with a history of stroke. However, the greater baseline level of cardiovascular risk in those with higher body mass index meant that these patients obtained the greatest benefit.
Hypertension 2010 May
PMID:Impact of blood pressure lowering on cardiovascular outcomes in normal weight, overweight, and obese individuals: the Perindopril Protection Against Recurrent Stroke Study trial. 2021 71

Blood flow reduction induces inward remodeling of resistance arteries (RAs). This remodeling occurs in ischemic diseases, diabetes and hypertension. Nonetheless, the effect of flow reduction per se, independent of the effect of pressure or metabolic influences, is not well understood in RA. As angiotensin II is involved in the response to flow in RA, we hypothesized that angiotensin II may also be involved in the remodeling induced by a chronic flow reduction. We analyzed the effect of angiotensin I-converting enzyme inhibition (perindopril) and angiotensin II type 1 receptor blockade (candesartan) on inward remodeling induced by blood flow reduction in vivo in rat mesenteric RAs (low flow (LF) arteries). After 1 week, diameter reduction in LF arteries was associated with reduced endothelium-dependent relaxation and lower levels of eNOS expression. Superoxide production and extracellular signal-regulated kinases 1/2 (ERK1/2 phosphorylation were higher in LF than in normal flow arteries. Nevertheless, the absence of eNOS or superoxide level reduction (tempol or apocynin) did not prevent LF remodeling. Perindopril and candesartan prevented inward remodeling in LF arteries. Contractility to angiotensin II was reduced in LF vessels by perindopril, candesartan and the ERK1/2 blocker PD98059. ERK1/2 activation (ratio phospho-ERK/ERK) was higher in LF arteries, and this activation was prevented by perindopril and candesartan. ERK1/2 inhibition in vivo (U0126) prevented LF-induced diameter reduction. Thus, inward remodeling because of blood flow reduction in mesenteric RA depends on unopposed angiotensin II-induced contraction and ERK1/2 activation, independent of superoxide production. These findings might be of importance in the treatment of vascular disorders.
 ...
PMID:Involvement of angiotensin II in the remodeling induced by a chronic decrease in blood flow in rat mesenteric resistance arteries. 2053 14


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