VO measurement in WKY demonstrated the utility of this method to assess hind limb perfusion at rest and during calf muscle contraction. Although application to diseased models (OZR and SHR) demonstrated normal resting perfusion compared with contralateral limbs, a significant reduction in reserve capacity was uncovered with muscle stimulation. Administration of Ramipril and Losartan demonstrated significant improvement in functional arterial reserve.
After a 2-week placebo wash-out 1453 elderly hypertensive patients (65-89 years; sitting office DBP 90-109 mmHg and/or sitting office SBP 140-179 mmHg) were randomized to a 12-week double-blind treatment with olmesartan medoxomil 10 mg or ramipril 2.5 mg once-daily, up-titrated (20 and 40 mg olmesartan medoxomil; 5 and 10 mg ramipril) after 2 and 6 weeks in patients without normalized office BP. 24-h ABP was recorded at randomization and after 12 weeks.
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In hypertensive patients, aliskiren-based treatment as well as ramipril-based treatment appears to have a beneficial effect on arterial stiffness. As arterial stiffness is an important modifiable risk factor, our findings highlight the value of aliskiren beyond BP lowering properties.
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The aim of this work was to study the effect of early administration of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type-I receptors blockers (ARB) on renal function and proteinuria in renal transplant recipients with good, stable renal function and mild proteinuria. Twenty four patients started ACEI/ARB therapy within 14 months after surgery (RAS-). Before (T0) and every month for 2 years after the initiation of ACEI/ARB we evaluated creatinine clearance (CrCl), proteinuria/day (UP), UP/CrCl (FUP), arterial blood pressure, and serum lipid levels. Twenty-eight patients who never received ACEI/ARB (RAS+) were studied in the same fashion. In the RAS+ CrCl was reduced after 2 years compared with T0 (64.5 +/- 2.6 vs 75.0 +/- 3.2 mL/min, P < .003); UP and FUP were both significantly increased (666 +/- 65 vs 132 +/- 20 mg/day 8.8 +/- 1.2 vs 2.6 +/- 0.6 mg/mL x 10(3); P < .001 and .002) compared with T0. Moreover, UP (P < .04), FUP (P < .03), and the percentage reduction of CrCl (11.4% +/- 5% vs 4.6% +/- 1.8%; P < .05) were greater in RAS+ than RAS- subjects at 2 years of the study. The values of other parameters did not show significant differences between the two groups. In conclusion, this study suggested that ACEI/ARB have renoprotective effects, when used in patients with good stable renal function and mild proteinuria. These drugs may play a role to prevent chronic allograft nephropathy.
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To explore the effect of Shen Shuai Fang in treating Chronic Renal Failure (CRF) of deficiency of spleen and kidney with turbid damp and blood stagnation symptom.
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Antihypertensive treatment resulted in an increase of PAP, vWf and sTM. During the first exercise, PF1+2 were mildly increased at peak exercise (p<0.05), while D-dimers, PAP and vWf varied significantly throughout the exercise (p<0.001). During the second exercise session, PF1+2 were decreased post-exercise (p<0.05), PAP was increased at peak and post-exercise (p<0.001) and vWf was increased at peak (p<0.05) and post-exercise (p<0.001).
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To investigate the hypothesis that prior angina pectoris confers protection from remodeling occurring after myocardial infarction (MI), we analyzed echocardiograms from the Healing and Early Afterload Reducing Therapy (HEART) trial.
To explore the effects and mechanism of ShenQi Compound Recipe on inflammation maker of type 2 diabetes mellitus in GK rats.
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The response to ramipril, 10 and 20 mg on consecutive days, in 9 patients with severe (New York Heart Association functional class III or IV) chronic congestive heart failure was measured. Hemodynamic cannulae were placed more than 2 days before ramipril administration to ensure a stable baseline. Dietary sodium (40 mmol daily) and potassium (80 mmol daily) were constant before and during the study, and maintenance doses of digoxin and furosemide (80 to 1,000 mg daily) were continued unchanged. Ramipril induced pronounced, sustained decreases in angiotensin converting enzyme activity, angiotensin II and aldosterone levels, and a reciprocal increase in plasma renin activity. Plasma catecholamines, antidiuretic hormone and cortisol levels were not altered. Urinary sodium and potassium excretion diminished, plasma sodium decreased and plasma potassium increased. Plasma urea and creatinine levels increased. Ramipril treatment resulted in a decrease in systemic arterial pressure that was sustained for 24 hours, a decrease in heart rate and an increase in cardiac index, but little change in pulmonary artery pressure or right atrial pressure. Three patients were drowsy after ramipril administration, and 1 patient had a marked, temporary reduction in urine output. It was concluded that ramipril is a potent, long-acting angiotensin converting-enzyme inhibitor that is likely to be beneficial in patients with severe cardiac failure.
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We present an overview of the differences in intakes of both water and NaCl between different strains of rat, with emphasis on Fischer 344 (F344) and Sprague-Dawley (SD) strains. Relative to SD, rats of the F344 strain show less spontaneous or secondary drinking both with food present and during food deprivation. The water intake of rats of the F344 strain is strongly inhibited when water is added to their food, but rats of the SD strain show less inhibition and consume excessive amounts of fluid. In studies of primary drinking, induced by treatment with various dipsogens, rats of the F344 strain consumed water in amounts that were generally comparable to those expected from rats of the SD strain, with the exception of reduced intakes in response to either polyethylene glycol-induced hypovolemia or treatment with isoproterenol. The hematocrit ratio, resting plasma renin activity and directly-measured plasma protein concentrations were similar between F344 and SD strains. We also review findings that rats of the F344 strain show no spontaneous preference for dilute NaCl solutions, and show that both a strong preference and a low preference threshold are induced by chronic treatment with ramipril. Other manipulations that induce an appetite for NaCl in the F344 strain are summarized.
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To investigate the roles of the cGMP-dependent protein kinases (cGKs) in the control of the renin system, we studied the regulation of renin in cGKI- or cGKII-deficient mice in vivo and in vitro. Renal renin mRNA levels both under stimulatory (low-salt diet plus ramipril) and inhibitory (high-salt diet) conditions were not different between wild-type and cGKI-/- mice, but were significantly elevated in cGKII-/- mice under all experimental conditions. In primary cultures of renal juxtaglomerular cells (JG) established from wild-type, cGKI-/-, and cGKII-/- mice, the adenylate cyclase activator forskolin stimulated renin secretion similarly in all genotypes tested. 8-bromo-cGMP attenuated basal and forskolin-stimulated renin secretion in cultures from wild-type and cGKI-/-, but had no effect in cells isolated from cGKII-/- mice. Activation of cGKs by 8-bromo-cGMP decreased renin secretion from the isolated perfused rat kidney, independent of prestimulation by beta-adrenoreceptor activation, macula densa inhibition, reduced perfusion pressure, or by a nominally calcium-free perfusate. Taken together, these findings suggest that activation of cGKII has a general inhibitory effect on renin secretion from renal JG cells.
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The CORD trials tested ramipril and losartan in patients with hypertension.
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The objective of the present-study was to determine whether acute inhibition of angiotensin converting enzyme (ACE), normalizes intrarenal sodium handling, renal haemodynamics and renal dopamine output in response to an i.v. NaCl infusion in type 1 diabetic patients with early nephropathy. Nine diabetic patients (aged 28 +/- 3 years) with elevated urinary albumin excretion (173 +/- 39 mg.min-1) were studied. The effects of a 2-hour NaCl infusion (12.5 ml.kg-1-h-1) on para-amino hippuric acid (PAH), insulin, lithium and sodium clearances as well as the urinary dopamine excretion were studied before and after 2 days of acute ACE inhibition. Fifteen healthy subjects (aged 34 +/- 1 years) served as controls. The results showed that 2 days of ACE inhibition improved the natriuretic response significantly (P < 0.05) within the first 2 h following an i.v. NaCl load due to a normalization of the proximal tubular sodium handling. In control subjects urinary dopamine output increased by 14% (P < 0.01) following i.v. NaCl infusion, whereas a blunted increase was seen in the diabetic patients, which tended to normalize following inhibition of ACE. In conclusion, this study demonstrates that patients with type 1 diabetes and early nephropathy display abnormalities in renal haemodynamics, natriuresis and urinary dopamine mobilization in response to a sodium load, which can be reversed by short-term inhibition of ACE.
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Early administration of zofenopril following acute myocardial infarction (AMI) proved to be prognostically beneficial in the four individual randomised, double-blind, parallel-group, prospective SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies. In the present analysis, we evaluated the cumulative efficacy of zofenopril by pooling individual data from the four SMILE studies.
A daily single capsule (polycap) of 3 blood pressure (BP) lowering drugs (hydrochlorthiazide, 12.5 mg; atenolol, 50 mg; ramipril, 5 mg) at low doses, simvastatin (20 mg), and aspirin (100 mg) has been demonstrated to be well tolerated and to reduce BP and low-density lipoprotein cholesterol. We examined the incremental effects of 2 (full dose) plus K(+) supplementation versus single polycap (low dose) on risk factors and tolerability.
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Plasma-thrombomodulin might be a useful marker for assessing the efficacy of drugs potentially protecting the vessel wall. While the present study was a open, non randomized study, further investigation is necessary to proof the hypothesis in a randomized, placebo-controlled, double-blind study.
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A 57-year-old white woman was found to have profound prolongation of her prothrombin time (56.9 sec) and international normalized ratio (22.18), with other coagulation parameters relatively normal. She had no prior history of bleeding diatheses and was not taking any prescribed anticoagulants. Her coagulopathy rapidly corrected with the administration of fresh frozen plasma and vitamin K. After her medications were visually inspected, it was discovered that she had purchased her prescription medications from a pharmacy in Mexico and that she inadvertently had been taking a preparation of warfarin (proprietary name in Mexico, "Romesa") instead of the prescribed ramipril for her hypertension (proprietary name in Mexico, "Ramace"). After removal of the incorrect medication, she experienced no further prolongation of her coagulation parameters.
Multiple switches per prescription are uncommon and multiple different products are rarely supplied on repeats of the same prescription. The rules of the brand substitution policy appear to be adequate in allowing brand choice for patients, without leading to multiple switches per prescription.
The acute cardiac effects of lixisenatide were investigated in isolated rat hearts subjected to brief ischemia and reperfusion. Effects of chronic treatment with lixisenatide on cardiac function were assessed in a modified rat heart failure model after only transient coronary occlusion followed by long-term reperfusion. Freshly isolated cardiomyocytes were used to investigate cell-type specific mechanisms of lixisenatide action.