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

We have previously established the existence of atrial natriuretic factor (ANF) gene expression within the renal parenchyma. Neither the role nor the regulation of this extracardiac source of ANF is clearly defined. To determine whether renal ANF gene expression, similar to cardiac expression, is linked to the activity of the renin-angiotensin system (RAS), we compared renal ANF gene expression in rats after suprarenal aortic banding, a hypertension model associated with activation of RAS, and in the deoxycorticosterone acetate (DOCA)-salt model, which is characterized by depression of RAS. Renal ANF mRNA was measured with a quantitative competitive reverse transcription polymerase chain reaction method. DOCA-salt hypertension significantly reduced the expression of renal ANF. In contrast, aortic banding significantly increased renal ANF expression. In both cases, ANF gene expression in the heart increased. Ramipril treatment at 10 micrograms/kg of aortic-banded rats, a treatment that specifically affects local RAS but maintains hypertension, normalized renal ANF mRNA levels. Altogether, these results suggest that renal ANF gene expression is modulated by local RAS and is independent of circulating RAS and hypertension per se. The marked decrease of renal ANF mRNA in DOCA-salt hypertension suggests a pathogenic role for renal ANF gene downregulation by decreasing the sodium excretory mechanism mediated by the local expression of ANF acting on receptors found in the inner medullary collecting ducts. In aortic banding, renal ANF gene expression upregulation suggests a local compensatory function consistent with the consensus role of natriuretic peptides in the modulation of RAS, thus ameliorating the sodium-retaining effects of renal underperfusion.
Hypertension 1999 Jun
PMID:Variable renal atrial natriuretic factor gene expression in hypertension. 1037 13

The objective of the study was to examine the influence of angiotensin converting enzyme (ACE) inhibition on circulatory responses to standardized stress tests in primary mild to moderate hypertension. Patients (n = 28) received 5 mg ramipril daily or placebo for 6 weeks in a double-blind crossover design, followed by 6 months of open ramipril treatment. Mental stress (a 20-min Stroop's color word conflict test) and a cold pressor test were performed at the end of each of the three study periods. Noninvasive blood pressure and heart rate were recorded. Ramipril reduced systolic and diastolic blood pressure levels at rest (from 146+/-3/99+/-3 with placebo to 135+/-4/94+/-3 at 6 weeks, and 136+/-4/91+/-3 mm Hg at 6 months, in the laboratory) and during mental stress. Resting heart rates were unchanged by ramipril. Ramipril reduced systolic blood pressure and heart rate responses during mental stress; diastolic blood pressure responses were unchanged. Ramipril reduced cardiac workload (systolic blood pressure x heart rate) levels and responses. Treatment effects at 6 months were generally greater than at 6 weeks. During the cold pressor test systolic and diastolic blood pressure levels were lowered by ramipril, but responses were unchanged. Heart rate responses, however, were reduced. Thus, ramipril reduced cardiac workload levels and responses also during the cold pressor test. These findings show that ACE inhibitors can reduce cardiac workload during stressful situations. If confirmed, this would seem to offer an advantage in the treatment of hypertension.
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PMID:The influence of long-term ACE inhibitor treatment on circulatory responses to stress in human hypertension. 1061 81

The Ramipril Efficacy in Nephropathy (REIN) study found that angiotensin-converting enzyme (ACE) inhibitors effectively decreased proteinuria, glomerular filtration rate (GFR) decline (DeltaGFR), and incidence of end-stage renal disease (ESRD) in patients with proteinuric chronic nephropathies. In this study, we prospectively investigated the main clinical determinants of progression and response to treatment in the 352 patients enrolled into the REIN study. Mean DeltaGFR (0.56 +/- 0.05 [SEM] versus 0.21 +/- 0.05 mL/min/1.73 m(2)/mo; P = 0.0001) and incidence of ESRD (30% and 10%; P = 0.0001) were more than twice that in patients with proteinuria of 2 g/24 h or greater of protein compared with those with protein less than 2 g/24 h (relative risk [RR], 4.07; 95% confidence interval [CI], 2.20 to 7.52), as well as in patients with hypertension compared with normotension (mean DeltaGFR, 0.48 +/- 0. 05 versus 0.22 +/- 0.05 mL/min/1.73 m(2)/mon; P = 0.0006; ESRD, 25% versus 10%; P = 0.004; RR, 3.18; 95% CI, 1.38 to 7.32). Hypertension at study entry (P = 0.038), greater mean blood pressure on follow-up (P = 0.002), and urinary protein excretion rate (P = 0.0001) were independent predictors of faster DeltaGFR. DeltaGFR was approximately twofold faster in patients with type 2 diabetes than in those with primary glomerular disease (P = 0.002; including immunoglobulin A [IgA] nephropathy, P = 0.009); nephrosclerosis (P = 0.03), adult polycystic kidney disease (APKD), or chronic interstitial nephritis (P = 0.006). Diabetes at study entry (P = 0. 02) and greater mean blood pressure (P = 0.0001) and urinary protein excretion rate (P = 0.0001) on follow-up were independent predictors of faster DeltaGFR. After correction for baseline covariates, diabetes was also associated with an increased risk for progression to ESRD (RR, 2.39; 95% CI, 1.01 to 5.68; P < 0.05). At multivariate analyses, ramipril significantly decreased DeltaGFR (regression coefficient,-0.23 +/- 0.11 [SEM]; P = 0.036) and ESRD (RR, 2.08; 95% CI, 1.21 to 3.57; P = 0.008) in patients with baseline proteinuria of 2 g/24 h or greater of protein, and the renoprotective effect increased for increasing levels of proteinuria. Ramipril decreased DeltaGFR to a similar extent in normotensive and hypertensive patients (-0.14 +/- 0.11 versus -0.14 +/- 0.09) and significantly limited ESRD in hypertensive patients (RR, 2.03; 95% CI, 1.26 to 3. 26; P = 0.004). DeltaGFR was decreased by 42% in primary glomerular disease (P = 0.017), by 35% in IgA nephropathy, and by 37% in nephrosclerosis, but was not improved in type 2 diabetes, APKD, or interstitial nephritis. At multivariate analyses, ramipril significantly slowed DeltaGFR (-0.24 +/-0.08; P = 0.004) and progression to ESRD (RR, 2.32; 95% CI, 1.36 to 3.96; P = 0.002) in patients without diabetes, but not in patients with diabetes, who tended to have a faster DeltaGFR (+0.62 +/- 0.44) on ramipril therapy. In summary, patients with proteinuria of 2 g/24 h or greater of protein, preexisting hypertension, or type 2 diabetes were faster progressors. Greater blood pressure and degree of proteinuria were the strongest determinants of faster GFR decline. The renoprotective effect of ramipril was similar in patients with normotension and hypertension. Hypertensive patients and those with proteinuria of 2 g/24 h or greater of protein, primary glomerular disease, or nephrosclerosis gained the most from ACE inhibitor treatment. During the study period, those with proteinuria less than 2 g/24 h of protein, type 2 diabetes, or polycystic kidney disease did not benefit by treatment to an appreciable extent.
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PMID:Chronic proteinuric nephropathies: outcomes and response to treatment in a prospective cohort of 352 patients with different patterns of renal injury. 1084 31

Ramipril is a long-acting, lipophylic angiotensin converting enzyme inhibitor, its principle action is to inhibit the conversion of angiotensin I to the active angiotensin II. Ramipril is indicated in the treatment of hypertension, congestive cardiac failure (including that following acute myocardial infarction), nephropathy (with and without diabetes mellitus) and now, following the findings of the HOPE study, in the prevention of cardiovascular events (including myocardial infarction) in high risk individuals. This article concentrates on reviewing the evidence supporting ramipril's use in these indications.
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PMID:Ramipril. 1091 16

Most chronic nephropathies are characterized by a progressive decline in glomerular filtration rate (GFR) that may lead to renal function replacement by dialysis or transplant. Hypertension has an extremely important role among the various mechanisms contributing to renal function deterioration. High blood pressure levels are associated with increased urinary excretion of proteins and the decrease of systemic and glomerular hypertension reduces urinary excretion of proteins and preserves renal function deterioration. Moreover, recent studies found that an intensified blood pressure control (less than 130/80 mmHg) can slow the progression of diabetic and non diabetic renal disease even more than conventional blood pressure control. The Ramipril Efficacy in Nephropathy (REIN) Study showed that ramipril, an ACE-inhibitor, slowed the rate of GFR decline and halved the combined risk of doubling serum creatinine or end stage renal failure (ESRF) in patients with nephrotic range proteinuria as compared to conventional antihypertensive therapy, at comparable levels of blood pressure control. In these patients, prolonged enough treatment (at least 36 months) with ramipril, lowered the velocity of GFR decline and reduced the risk of dialysis. Thus, both tight blood pressure control and ACE-inhibitors may have a renoprotective effect. It will be interesting to evaluate whether the two combined approaches may have sinergistic effects.
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PMID:How much must blood pressure be reduced in order to obtain the remission of chronic renal disease? 1092 1

Over a 4.5 year follow-up period, the HOPE (Heart Outcomes Prevention Evaluation) trial, and the MICRO-HOPE (Microalbuminuria, Cardiovascular, and Renal Outcomes) and SECURE (Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E) substudies have all demonstrated a large benefit of ramipril versus placebo in patients over 55 years at high risk (by reason of a prior vascular event), or by being diabetic subjects with one additional risk factor. The baseline blood pressure on average was normal, at 139/79 mmHg, and was modestly reduced by 3.3/1.4 mmHg. Patients with known left ventricular dysfunction were excluded, as were those with uncontrolled hypertension. The incidence of stroke was reduced by 32%, myocardial infarction by 20% and cardiovascular death by 25%. The benefits conferred were in addition to, and largely independent of, other conventional treatments such as aspirin, lipid-lowering agents, beta-blockers, diuretics and calcium channel blockers. The relative risk reduction was very similar whether or not the patient was a known hypertensive at baseline. High dose ACE inhibition with ramipril is applicable to a far wider population of patients at high risk of cardiovascular events than the current indications of hypertension and left ventricular dysfunction.
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PMID:Future perspectives and implications. 1171 55

In the HOPE-trial, the ACE inhibitor ramipril significantly reduced cardiovascular morbidity and mortality in patients at high risk for cardiovascular events. The benefit could only partly be attributed to the modest mean reduction of office blood pressure (OBP) during the study period (3/2 mm Hg). However, because according to the HOPE protocol ramipril was given once daily at bedtime and blood pressure was measured during the day, the 24-hour reduction of blood pressure may be underestimated based on OBP. Thirty-eight patients with peripheral arterial disease enrolled in the HOPE study underwent 24-hour ambulatory blood pressure (ABP) measurement before randomization and after 1 year. OBP was measured in the sitting position immediately before fitting the ABP measuring equipment to the patients. Ramipril did not significantly reduce OBP (8/2 mm Hg, P=NS) or day ABP (6/2 mm Hg, P=NS) after 1 year. Twenty-four-hour ABP was significantly reduced (10/4 mm Hg, P=0.03), mainly because of a more pronounced blood pressure lowering effect during nighttime (17/8 mm Hg, P<0.001). The night/day ratio was also significantly lowered in the ramipril group. ABP shows greater falls, especially at night, than OBP during treatment with ramipril given once daily at bedtime. Although, OBP is the correct comparator when comparing with previous large intervention trials and epidemiological studies, the effects on cardiovascular morbidity and mortality seen with ramipril in the HOPE study may, to a larger extent than previously ascribed, relate to effects on blood pressure patterns over the 24-hour period.
Hypertension 2001 Dec 01
PMID:Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE Substudy. 1262 66

Proven cardiovascular benefit from angiotensin-converting enzyme (ACE) inhibition is a cornerstone of evidence-based medicine. The first study to show dramatic benefits from ACE inhibition was the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS-I), in which a 31% decrease in the rate of death was observed in patients with severe heart failure at the end of 1 year of enalapril treatment (p = 0.001). This result led to large long-term studies-including Survival and Ventricular Enlargement (SAVE), Acute Infarction Ramipril Efficacy (AIRE), Trandolapril Cardiac Evaluation (TRACE), and Study of Left Ventricular Dysfunction (SOLVD)-which verified that ACE inhibition decreases heart failure, myocardial infarction (MI), and mortality, and that striking benefit could be observed within 30 days. Short-term studies of patients in the acute phase of a heart attack verified that ACE inhibition provided rapid benefits. A meta-analysis of short-term (up to 8 weeks) studies of ACE inhibition (including CONSENSUS-II, Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico [GISSI]-3, International Study of Infarct Survival [ISIS]-4, and the Chinese Captopril Study [CCS]-1) demonstrated that post-MI risk was reduced by 10% within the first day of treatment. The immediacy of the benefit suggested that ACE inhibition not only improved cardiovascular function in failing hearts but also affected important mechanisms in patients without overt heart failure. Effects on more general mechanisms of heart disease suggested that patients with problems other than hypertension or heart failure might benefit from ACE inhibitors. The Heart Outcomes Prevention Evaluation (HOPE) study investigated the hypothesis that ACE inhibition would confer benefits to patients who were at high risk for cardiovascular events, but who were without left ventricular dysfunction or heart failure. Long-term reductions in MI, stroke, cardiac arrest, and heart failure, as well as improvements in mortality, were observed in this population after treatment with ACE inhibitors. Substudies of the HOPE study revealed that ACE inhibition reduced progression of atherosclerosis and improved myocardial remodeling. Taken together, these studies provide evidence that supports treatment of a broad population of patients at risk for cardiovascular events with ACE inhibitors. The next step is to combine ACE inhibition with other treatments to maximize patient benefit. The Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) will compare the efficacy of an ACE inhibitor (ramipril) with an angiotensin receptor blocker (telmisartan), and determine whether these treatments in combination will further reduce morbidity and mortality from cardiovascular disease.
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PMID:Angiotensin II and trials of cardiovascular outcomes. 1183 5

Experimental and clinical evidence suggest that angiotensin converting enzyme (ACE) inhibition may reduce cardiovascular (CV) risk by directly affecting endothelial dysfunction, atherosclerosis and thrombus formation. These direct effects are in addition to effects on vascular tone or pressure. The Health Outcomes and Prevention Evaluation (HOPE) study assessed the role of an ACE inhibitor ramipril in reducing CV events in 9297 patients > or = 55 years who were at high risk of CV events but did not have left ventricular dysfunction, heart failure, or high blood pressure at the time of study entry. In the overall HOPE population, the risk of the primary composite outcome (cardiovascular death, myocardial infarction, or stroke) was reduced by 22% (p < 0.001), and in patients with diabetes plus one other CV risk, it was reduced by 25% (p = 0.0004). Ramipril treatment achieved risk reduction in patients with mild renal insufficiency (serum creatinine > or = 1.4 mg/dl). Ramipril treatment did not increase adverse events in patients with renal insufficiency. The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and Vitamin E (SECURE) demonstrated that ramipril 10 mg significantly reduced the rate of carotid intimal medial thickening, suggesting a direct effect on atherosclerotic progression.
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PMID:What should the role of ACE inhibitors be in the treatment of diabetes? Lessons from HOPE and MICRO-HOPE. 1184 51

Given the significant public health impact of stroke and the identification of nonmodifiable (age, gender, race/ethnicity) and modifiable (blood pressure, diabetes, lipid profile, and lifestyle) risk factors, early prevention strategies should be initiated. When a patient suffers a stroke, the focus of care becomes prevention of future events. For the patient with diabetes, comprehensive medical management of ischaemic stroke (primary or secondary prevention) includes antihypertensive and lipid-lowering therapy, as well as antiplatelet therapy. Despite the cerebrovascular risk reduction with these modalities, clearly new agents are needed. The Heart Outcomes Prevention Evaluation (HOPE) study provides compelling evidence that treatment with the angiotensin converting enzyme inhibitor, ramipril, can further reduce the risk of stroke in high-risk patients by mechanisms other than lowering blood pressure. In HOPE, patients were normotensive at baseline. Therefore, for the first time, in a patient population without left ventricular dysfunction, the effects of an ACE inhibitor ramipril on reducing stroke risk were demonstrated. Ramipril 10 mg achieved a significant 33% reduction in stroke among patients with diabetes. Based on the HOPE study, the recently published American Heart Association guidelines for the primary prevention of stroke recommend ramipril to prevent stroke in high-risk patients and in patients with diabetes and hypertension. Wide-scale adherence to these guideline recommendations for the prevention of primary and secondary stroke would significantly benefit the public health.
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PMID:Reducing the risk of stroke in diabetes: what have we learned that is new? 1184 52


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