UMLS:C0020538 - FACTA Search

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)

The Heart Outcomes Prevention Evaluation (HOPE) study was designed to test the hypotheses that two preventive intervention strategies, namely angiotensin-converting enzyme (ACE) inhibition or vitamin E, would improve morbidity and mortality in patients at high risk of cardiovascular events compared with placebo. This review addresses the ACE inhibitor (ACE-I) (ramipril) arm of the study, both on the trial population as a whole, and on the large diabetic subgroup. Patients were included in the study who were considered to be at high risk of future fatal or non-fatal cardiovascular events, by virtue of their age (>55 years), existing or previous cardiovascular disease, or diabetes. Diabetics had at least one other risk factor, either known vascular disease or other factors such as cigarette smoking, high cholesterol or hypertension. Ramipril or placebo was added to concomitant medication, which included, in a substantial proportion of patients, antihypertensive drugs (excluding ACE-I), lipid-lowering agents or aspirin. As a result, despite a history of hypertension in nearly 50% of patients, blood pressure (BP) at baseline was normal and the reduction in BP attributable to ramipril modest (a fall of 3-4 mmHg systolic BP and 1-2 mmHg diastolic). The trial was stopped early on the advice of the Data Monitoring Committee because of convincing evidence of the benefit of ramipril treatment on the combined primary endpoint of cardiovascular death, non-fatal myocardial infarct (MI) and non-fatal stroke (14% vs. 17.8% on ramipril and placebo, respectively; relative risk reduction 22%, p<0.001). This comprised a risk reduction of 32% for stroke, 20% for MI, 26% for cardiovascular death and 16% for all-cause mortality, as well as a reduction in the risk of several other endpoints including heart failure and revascularisation procedures. The results among the 3577 diabetic subjects were even more striking, with a reduction of 25% in the combined primary endpoint. This reduction in the combined endpoint and in particular the reduction in MI far exceeded that which would be expected from the modest fall in BP. Furthermore, a multiple regression analysis of the diabetic subgroup showed similar relative risk reductions even after allowing for the effects of the fall in BP. Possible explanations for the non BP-mediated benefits of ramipril include reduction of angiotensin II-induced intimal and vascular smooth muscle proliferation and possible plaque stabilisation. The HOPE study results show that it is both safe and beneficial to lower BP that is already within the 'normal' range, particularly in patients with known vascular risk factors. This should greatly extend the use of ACE-I to a wider group of patients - not only those with left ventricular dysfunction, hypertension or diabetic microalbuminuria, but to the sort of high-risk patients who are currently given prophylactic treatment with aspirin.
...
PMID:The HOPE Study (Heart Outcomes Prevention Evaluation). 1196 89

Antihypertensive treatment reduces the risk of thromboembolic events in hypertension. The aim of this study was to examine the influence of angiotensin-converting enzyme inhibition on blood coagulation in subjects with mild-to-moderate essential hypertension. Fibrinogen, thrombin-antithrombin complex (TAT) and Factor VII were determined in plasma at rest and after a mental stress test following placebo for 6 weeks, or ramipril for 6 weeks or 6 months. Ramipril reduced resting TAT, and tended to reduce fibrinogen; Factor VII remained unchanged. Mental stress increased fibrinogen, but did not alter TAT or Factor VII activity. The reduced thrombin generation in patients taking ramipril may explain in part why angiotensin-converting enzyme inhibitors reduce thromboembolic complications in patients with cardiovascular disease.
...
PMID:Long-term angiotensin-converting enzyme inhibition with ramipril reduces thrombin generation in human hypertension. 1214 6

To explore the effect of angiotensin converting enzyme (ACE) inhibitor on apoptosis in spontaneously hypertensive rats(SHR), and normotensive control rats (WKY) at different ages were used. Ramipril (1 mg.kg-1.d-1) was administered orally to male SHR from 3 or 5 weeks to 10 weeks of age. Male and age-matched untreated SHR and WKY were used as controls. Experiments determined. Apoptosis in cardiomyocytes of SHR was quantified by a maximal labeling (Lmax) method and the characteristic features of apoptosis were identified by electron microscopy (EM), in situ labeling of DNA strand breaks with terminal deoxynucleotidyl transferase mediated dUTP end labeling (TUNEL) and autoradiographic analysis of DNA fragments. The results of the quantitative method showed an age-dependent increase in apoptosis in the cardiac tissues of SHR. A significant increase in DNA breaks occurred as early as age 4 weeks and continued to increase up to a plateau at age 16 weeks in the cardiac tissue of SHR, whereas there was no significant change in apoptosis in WKY up to 64 weeks. Moreover, after the treatment of SHR with ramipril, an inhibitor of ACE, the DNA fragmentation, like BP and HW/BW, was reduced significantly (70.7%) as compared with that of untreated SHR(P < 0.01); and similar to that of the WKY (P > 0.1), the DNA ladder disappeared, which was very obvious in the untreated SHR. These studies demonstrate that ramipril can prevent the development of hypertension and myocardial hypertrophy and can inhibit the increase in the apoptosis of SHR cardiac myocytes, suggesting that apoptosis may be involved in the pathogenesis of genetic hypertension.
...
PMID:[Investigation of inhibitory effect of ramipril on apoptosis in spontaneously hypertensive rats]. 1220 19

Drugs that inhibit the renin-angiotensin system (RAS) are of proven benefit in the treatment of hypertension, congestive heart failure, or acute myocardial infarction. In the last decade, several clinical trials have shown that RAS inhibitors also offer significant renoprotection in both diabetic and non-diabetic nephropathy. However, patients with advanced renal insufficiency did not take part in these trials because of the risk of acute renal failure (ARF) and hyperkalemia, and, for the same reason, most physicians do not offer these drugs to patients with impaired renal function. Recently, a post-hoc analysis of the Ramipril Efficacy In Nephropathy (REIN) study which included patients with severe renal insufficiency, showed that RAS inhibition slows glomerular filtration rate (GFR) decline over time and progression to end-stage renal disease (ESRD) in a safe way in patients quite close to ESRD (basal GFR, 10 to 30 ml/min/1.73m2). These beneficial effects have also been shown in the Reduction of Endpoints in NIDDM with the All Antagonist Losartan (RENAAL) study, in patients with type 2 diabetes mellitus, clinical proteinuria, and renal insufficiency, where RAS inhibition therapy significantly reduced the risk of ESRD once doubling of baseline serum creatinine levels had been achieved as compared to non-RAS anti-hypertensive treatment. Thus, these data suggest that RAS inhibition therapy should be given to all patients with proteinuric chronic nephropathy, independently of the level of renal function.
...
PMID:Inhibitors of the renin-angiotensin system reduce the rate of GFR decline and end-stage renal disease in patients with severe renal insufficiency. 1224 75

In patients with cyclosporine-induced hypertension, upregulation of the nitric oxide system and oxidative stress were shown, which could induce hypertension, remodeling, and chronic rejection by increasing nitric oxide catabolism. However, it is still debated whether cyclosporine and tacrolimus exert a different action. The aim of the current study was to compare the effects of cyclosporine and tacrolimus on markers of oxidative stress and endothelial dysfunction in kidney transplant patients with posttransplant hypertension. Monocyte p22, a NADH/NADPH system subunit, transforming growth factor-beta (TGF-beta), heme oxygenase-1 (HO-1), and endothelial NOS gene expression were measured in 16 patients. Angiotensin II is a potent stimulator of oxidative stress and angiotensin-converting enzyme inhibition may blunt this effect. Therefore, the same parameters were measured before and after 2 months of treatment with ramipril (5 mg/d). At baseline, in cyclosporine-and tacrolimus-treated patients, p22 and TGF-beta mRNA were similarly increased in comparison with normotensive healthy controls (0.90 +/- 0.05 d.u. and 0.83 +/- 0.05 in cyclosporine, 0.89 +/- 0.07 and 0.84 +/- 0.05 in tacrolimus; 0.53 +/- 0.07 and 0.75 +/- 0.03 in controls, respectively; p < 0.001). Endothelial NOS mRNA was increased in cyclosporine-and tacrolimus-treated patients in comparison with controls (0.92 +/- 0.09, 0.96 +/- 0.04, and 0.37 +/- 0.05 respectively; p < 0.001), whereas no difference was found between patients and controls in HO-1 mRNA. Ramipril reduced blood pressure (from 140 +/- 11/91 +/- 7 mm Hg to 129 +/- 6/85 +/- 5 mm Hg in cyclosporine and from 138 +/- 7/92 +/- 7 mm Hg to 127 +/- 10/82 +/- 6 mm Hg in tacrolimus group; p < 0.02 with no difference between groups). Ramipril also reduced p22 (to 0.83 +/- 0.05 in cyclosporine, p < 0.03 and to 0.81 +/- 0.08 in tacrolimus; p < 0.01) and TGF-beta mRNA (to 0.72 +/- 01 in cyclosporine, p < 0.02, and to 0.73 +/- 0.05 in tacrolimus; p < 0.01) with no difference between groups, but it did not change HO-1 and ecNOS mRNA. Cyclosporine and tacrolimus induce a comparable oxidative stress in kidney transplant patients with posttransplant hypertension. The association of ramipril normalizes blood pressure and reduces the oxidative stress induced by both drugs.
...
PMID:Oxidative stress in kidney transplant patients with calcineurin inhibitor-induced hypertension: effect of ramipril. 1235 26

Numerous studies have emphasized the important role of altered Ca(2+) channel function in hypertension. We previously showed that Ca(2+) currents measured in myocytes isolated from both Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) small mesenteric arteries closely correlated with systolic blood pressure (BP) during normal development. The purpose of the present experiments was to determine whether antihypertensive therapy with an angiotensin converting enzyme inhibitor normalizes Ca(2+) channel function in SHR myocytes along with BP. Ramipril (3.5 mg/kg/day) was added to the drinking water of 12-week-old male WKY and SHR for 8 weeks. Segments of small mesenteric arteries were used for isometric contraction studies, and for isolation of myocytes for measurement of Ca(2+) and K(+) currents (I(Ca) and I(K)) by patch clamp methods. Ramipril treatment decreased systolic pressure in WKY and SHR, decreased heart weight and heart weight-to-body weight ratio in SHR, and decreased body weight in WKY. Maximum contractile responses to Bay k 8644 in SMA from ramipril-treated SHR were smaller compared to untreated SHR (10% +/- 2% v 55% +/- 7% of the response to 120 mmol/L KCl). The smaller responses in WKY were not affected by ramipril treatment (11% +/- 4% v 8% +/- 3%). Contractile responses to 10 mmol/L tetraethylammonium (TEA) were not different in untreated versus ramipril-treated SHR (65% +/- 6% v 82% +/- 8%) but were increased in treated WKY (4% +/- 1% v 35% +/- 9%). Ramipril treatment decreased peak I(Ca) and equalized the voltage-dependence of I(Ca) activation between SHR and WKY. The I(K) measured from holding potentials of -60 and -20 mV were significantly smaller in treated SHR and WKY compared to their untreated counterparts, as was the component of I(K) measured in the presence of 100 nmol/L iberiotoxin. These results show that ramipril treatment decreases arterial pressure and Ca(2+) channel function in SHR as expected but unexpectedly also decreases I(K) in both WKY and SHR. These results suggest that angiotensin may have a BP independent effect on ion channel function in arterial smooth muscle.
...
PMID:Ramipril treatment alters Ca(2+) and K(+) channels in small mesenteric arteries from Wistar-Kyoto and spontaneously hypertensive rats. 1237 75

ACE inhibition reduces plasminogen activator inhibitor-1 (PAI-1), a risk factor for myocardial infarction, whereas the effect of angiotensin receptor antagonism on PAI-1 is uncertain. The present study compares the time course of effects of ACE inhibition and angiotensin type 1 (AT1) receptor antagonism on morning plasma PAI-1 antigen. Blood pressure and endocrine, metabolic, and fibrinolytic variables were measured in 20 insulin-resistant (defined by fasting glucose >8.3 mmol/L, body mass index >28 kg/m2, or fasting serum triglyceride > or =2.8 mmol/L) hypertensive subjects (mean age, 47.9+/-2.1 years) (1) before and after 1 week of hydrochlorothiazide 12.5 mg/d, and (2) before and 1, 3, 4, and 6 weeks after addition of ramipril (escalated to 10 mg/d) or losartan (escalated to 100 mg/d). Hydrochlorothiazide decreased systolic (P=0.011) and diastolic (P=0.019) pressure. Ramipril (from 133.6+/-5.1/94.5+/-2.4 to 127.0+/-3.1/91.4+/-3.3 mm Hg) or losartan (from 137.0+/-3.9/93.1+/-2.9 to 123.7+/-2.6/86.4+/-2.1 mm Hg) further reduced systolic (P=0.009) and diastolic (P=0.037) pressure. The pressure effects of the 2 drugs were similar. Hydrochlorothiazide increased plasma PAI-1 (P=0.013) but not tissue-type plasminogen activator (tPA) (P=0.431) antigen. Addition of either ramipril or losartan significantly decreased plasma PAI-1 antigen (P=0.046). However, the effect of losartan on PAI-1 antigen was not sustained throughout the 6-week treatment period, such that there was a significant drugxtime interaction (P=0.043). tPA antigen decreased during either ramipril or losartan (P=0.032), but tPA activity decreased only during losartan (P=0.018). Short-term interruption of the renin-angiotensin-aldosterone system by either ACE inhibition or AT1 receptor antagonism decreases PAI-1 antigen, but the duration of this effect is greater for ACE inhibition than for AT1 receptor antagonism.
Hypertension 2002 Dec
PMID:ACE inhibition versus angiotensin type 1 receptor antagonism: differential effects on PAI-1 over time. 1246 70

The circulation in the left and right coronary beds in pressure overload-induced left ventricular (LV) hypertrophy was studied in Wistar male rats (n=6/group) that were subjected to abdominal aortic constriction or to sham-operation. From 3 to 6 weeks after surgery, the animals with aortic constriction received vehicle or 0.01, 0.1, or 1 mg/kg per day po of the angiotensin converting enzyme (ACE) inhibitor, ramipril. At 6 weeks, after measuring blood pressure in the carotid artery in vivo, the hearts were isolated and the left and right coronary beds subjected to independent perfusion. Minimum coronary vascular resistance per unit heart weight (MCVR/g) was determined in both beds during simultaneous infusion of 10 micromol/L adenosine. Aortic constriction resulted in a significant increase in blood pressure, LV weight/body weight ratio, and bilateral MCVR/g. Ramipril lowered arterial pressure in a dose-dependent manner and reversed the increased right MCVR/g at the anti-hypertensive dose, but it did not affect LV mass or left MCVR/g. These results suggest that both coronary hypertension and myocardial hypertrophy contribute to the global impairment of coronary circulation in LV hypertrophy. ACE inhibitors may improve coronary circulation in LV hypertrophy when administrated at an appropriate dose and for a sufficient period.
...
PMID:Left and right coronary circulation in left ventricular hypertrophy: effects of angiotensin converting enzyme inhibition. 1249 26

Incidence of CVD in diabetic men was reported to be twice as that of non-diabetics and almost three times greater in diabetic women in the Framingham Study. It is postulated that excessive glycation and oxidation, endothelial dysfunction and increased platelet aggregation may be responsible for endothelial proliferation and thickening of plasmatic membrane in small blood vessels ('lipohyalinosis') leading to lacunar infarction. Prothrombotic state may precipitate a stroke, however, platelet aggregability, elevated fibrinopeptide A (FPA) and D-dimer were not significantly related to stroke in diabetic mellitus (DM), whereas suppressed fibrinolytic activity was a common finding. Of many unknown factors in pathogenesis, the deficient insulin secretion, resistance to action of insulin at level of 'insulin receptors', changes in counter regulatory hormones (e.g. glucagon, pancreatic polypetides, growth hormone, catecholamines, etc.) and decrease in the hepatic sensitivity to insulin action in suppressing glucose output have received more attention. Hyperosmolar state can simulate stroke syndromes. Early recognition and treatment of risk factors such as hypertension or better glycemic control, correction of hyperlipidemia or obesity in diabetic population are important. In diabetic subjects already showing recurrent transient cerebral ischemic attacks (TIAs) or minor strokes, the benefit of antiplatelet agents or antithrombotic therapy in prevention of major strokes is well established. Ramipril has been found to be effective in reducing stroke risk by 33% in diabetic patinets in HOPE study.
...
PMID:Cerebrovascular disease in type 2 diabetes mellitus. 1257 84

The aim of this work was to ascertain, in nonmodulating essential hypertension, whether the abnormality in the renal blood supply is extended to the extremities and showed a similar response to ACE inhibition and whether these abnormalities could be identified in normotensive offspring of hypertensives, as non-modulation is a familial process with genetic underpinnings. We measured forearm vascular blood flow (FBF) and forearm vascular resistance (FVR) by plethysmography and urinary albumin excretion in 20 normotensive without family story of hypertension (NT: 25+/-9 years), 10 modulating offspring of hypertensive parents (MHO: 25+/-6 years), 10 nonmodulating offspring of hypertensive parents (NMHO: 26+/-5 years), 12 modulating essential hypertensives (MHT: 34+/-5 years), and 11 nonmodulating essential hypertensives (NMHT: 32+/-4 years). Measurements were repeated in hypertensives after 3-month treatment with ramipril (5 mg daily). Nonmodulating individuals showed lower maximum FBF (NMHT: 41.96+/-3.3 mL/100 g per minute and NMHO: 35.6+/-9.0 mL/100 g per minute) than modulating subjects (MHT: 57.5+/-10.0 mL/100 g per minute and MHO: 51.8+/-7.0 mL/100 g per minute; P<0.003). Likewise, all nonmodulating subjects showed higher minimum FVR (NMHT: 2.5+/-0.2 AU; NMO: 2.8+/-0.5 AU) than modulating individuals (MHT: 1.9+/-0.5 AU; MHO, 1.8+/-0.3AU; P<0.025). Urinary albumin excretion was higher in NMHT and NMHO than MHT, MHO, and NT (P<0.05). Ramipril increased maximum FBF to 53.8+/-8.0 mL/100 g per minute and reduced minimum FVR to 1.9+/-0.5 AU in NMHT (P<0.01). Likewise, ramipril increased effective renal plasma flow and reduced renal vascular resistance and urinary albumin excretion only in NMHT (P<0.05). These results have shown an early involvement of the peripheral circulation in association with increased urinary albumin excretion not only in essential hypertensives but also in NMHO. The effectiveness of ramipril in reducing minimum FVR and urinary albumin excretion in NMHT also suggests a common mechanism.
Hypertension 2003 Apr
PMID:Parallel renal and extremity blood supply abnormalities in nonmodulation: responses to ACE inhibition. 1264 7

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