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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Blood pressure is an important determinant of the risk of macro- and microvascular vascular complications in patients with type 2 diabetes. Current European guidelines for the management of hypertension recommend lowering blood pressure in patients with type 2 diabetes to reduce the risk of cardiovascular events. The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial (n = 11,140), is the first trial designed to address the issue of whether routine blood pressure lowering with the fixed combination of perindopril/indapamide is beneficial in patients with diabetes with a broad range of baseline blood pressure values. In addition, it aimed to determine if clinical benefit is achieved over and above that observed with background angiotension-converting enzyme inhibitor therapy. In the perindopril/indapamide arm, the reduction in blood pressure led to significant clinical benefits in patients with type 2 diabetes, irrespective of baseline blood pressure values, and subsequently improved mortality rates, and macro- and microvascular outcomes, beyond the improvements associated with patients' existing antihypertensive therapies. ADVANCE is a robust well-designed trial, the results of which are directly applicable to current clinical practice. The ADVANCE study defines the relevant blood pressure goals for patients with type 2 diabetes who are at high risk of cardiovascular events and underscores the benefits of aggressive blood pressure reduction even in normotensive patients with diabetes. It is likely that these findings will have a significant impact on the management of patients with type 2 diabetes. In view of the evidence indicating that clinical benefits obtained with the perindopril/indapamide combination can be expected even in patients who are normotensive, vascular risk rather than initial blood pressure should be employed to determine appropriate treatment protocols in patients with type 2 diabetes.
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PMID:Implications of the ADVANCE study for clinical practice. 1936 50

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.
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PMID:Angiotensin-converting enzyme inhibition by perindopril in the treatment of cardiovascular disease. 1937 59

Cardiovascular disease is the predominant cause of death in diabetic patients, and reducing the risk of cardiovascular disease in diabetics has recently been the focus of several highly publicized large trials, including ACCORD (Action To Control Cardiovascular Risk in Diabetes), ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), and VADT (Veterans Affairs Diabetes Trial). These studies randomized high-risk diabetic patients into either intensive treatment or standard treatment. The glycemic control arm of ACCORD was terminated 17 months before the planned end of the study because of a finding of significantly increased all-cause and cardiovascular mortality in the intensive treatment group. These findings were not duplicated in either ADVANCE or VADT. Multiple possible explanations have been brought forward, including a higher incidence of death from unrecognized hypoglycemia, effects due to increased exposure to particular antidiabetic medications, adverse effects of rapid correction of hyperglycemia, weight gain, and differences in baseline characteristics. None of these were validated in post hoc analyses of the trial data, and the cause of the increased mortality remains elusive. Subgroup analyses suggest that those who start off with better control of their diabetes or without preexisting cardiovascular disease may have the most to gain from tight glycemic control. Reducing the risk of macrovascular disease and death in diabetic patients requires not only attention to glucose control but also meticulous attention to control of nonglycemic risk factors, including hypertension, hyperlipidemia, smoking, lack of exercise, and unhealthy diet as well as timely prescription of medications with proven preventative benefits, such as aspirin and statins.
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PMID:Glycemic targets for patients with type 2 diabetes mellitus. 1942 66

The relative importance of various blood pressure indices on cardiovascular risk in people with type 2 diabetes mellitus has not been established. This study compares the strengths of the associations between different baseline blood pressure variables (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP], and mean arterial pressure) and the 4.3-year risk of major cardiovascular events in the Action in Diabetes and Vascular Disease: Preterax and Diamicron-Modified Release Controlled Evaluation Study. Mean (SD) age for the 11 140 participants was 65.8 years (6.4 years). During follow-up, 1000 major cardiovascular events, 559 major coronary events, and 468 cardiovascular deaths were recorded. After adjustment for age, sex, and treatment allocation, the hazard ratios (95% CIs) associated with 1 increment in SD for the risk of major cardiovascular events were 1.17 (1.10 to 1.24) for SBP; 1.20 (1.13 to 1.28) for PP; 1.12 (1.05 to 1.19) for mean arterial pressure; and 1.04 (0.98 to 1.11) for DBP. The areas under the receiver operating characteristic curve were slightly higher for SBP and PP compared with mean arterial pressure and DBP for major cardiovascular and coronary events. Using achieved instead of baseline blood pressure values marginally improved the effect estimates for SBP, DBP, and mean arterial pressure, with no significant differences in the areas under the receiver operating characteristic curve between models with SBP and those with PP. In conclusion, SBP and PP are the 2 best and DBP is the least effective determinant of the risk of major cardiovascular outcomes in the relatively old patients with type 2 diabetes mellitus participating in the Action in Diabetes and Vascular Disease: Preterax and Diamicron-Modified Release Controlled Evaluation Study. However, SBP may be the simplest and most useful predictor across a wider range of age groups and populations.
Hypertension 2009 Aug
PMID:Blood pressure variables and cardiovascular risk: new findings from ADVANCE. 1947 Aug 69

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.
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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.
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PMID:Involvement of angiotensin II in the remodeling induced by a chronic decrease in blood flow in rat mesenteric resistance arteries. 2053 14

Angiotensin-converting enzyme (ACE) inhibitors have clinically been widely used as anti-hypertensive agents. In the present study, we compared the effects of a centrally active ACE inhibitor, perindopril, with those of non-centrally active ACE inhibitors, imidapril and enalapril, on cognitive performance in amyloid beta(Abeta) (25-35)-injected mice, a rodent model of Alzheimer's disease. We also determined the brain ACE activity in order to elucidate the relationship between the cognitive function and ACE inhibition in the brain. Abeta(25-35)-injected mice showed a cognitive impairment in spontaneous alteration and object recognition tests, the indices of immediate working memory and relatively long-term recognition memory, respectively. As indicated by these tests, the oral administration of perindopril (0.1, 0.3 or 1mg/kg/day) significantly reversed the cognitive impairment in these mice, whereas neither imidapril (0.3, 1 or 3mg/kg/day) nor enalapril (1, 3 or 10mg/kg/day) had any effect on cognitive performance. Perindopril (1mg/kg/day), imidapril (3mg/kg/day), or enalapril (10mg/kg/day) all inhibited the plasma ACE activities by more than 90%. Using the same dosing regimen, only perindopril inhibited the brain ACE activities by more than 50%, whereas imidapril and enalapril showed much less potent effects. These results suggest that perindopril ameliorated the cognitive impairment in the Alzheimer's disease model mice through the inhibition of brain ACE activity, but not peripheral ACE activity. Based on our observations, we concluded that a centrally active ACE inhibitor, perindopril, may therefore have a beneficial effect on Alzheimer's disease as well as hypertension.
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PMID:Effect of a centrally active angiotensin-converting enzyme inhibitor, perindopril, on cognitive performance in a mouse model of Alzheimer's disease. 2062 92


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