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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To establish if the benefit of angiotensin converting enzyme inhibitor therapy in retarding progressive diabetic renal injury is due to a specific intrarenal effect of the systemic hypotensive effect, we studied the effect of long-term ramipril treatment on blood pressure, glomerular filtration rate, and urinary protein excretion in streptozotocin-diabetic spontaneously hypertensive rats. The hypotensive effect of ramipril was prevented by a high salt diet, which did not alter the degree of renal angiotensin converting enzyme inhibition. Three weeks after uninephrectomy and induction of diabetes, rats were allocated to three groups. Groups 1 and 2 were given 1% NaCl, whereas group 3 was given water as drinking solution. One week later, groups 2 and 3 received 0.4 mg/kg/day ramipril in their drinking solution, which was continued over a 2-month period. Ramipril produced a blood pressure fall only in water-drinking rats (group 3) despite a similar reduction in plasma and renal angiotensin converting enzyme activity in groups 2 and 3. Salt-loaded rats had a progressive increase in urinary protein excretion over the duration of study. Ramipril treatment prevented an increase in protein excretion only in animals given water and with a reduced systolic blood pressure. Glomerular filtration rate was similar in all three groups. Ramipril treatment improved animal survival independently of a reduction in blood pressure or an effect on proteinuria. Although it is possible that angiotensin converting enzyme inhibitors have specific intrarenal effects reducing progression of diabetic proteinuria, concomitant control of systemic blood pressure appears to be necessary to demonstrate a benefit.
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PMID:Salt blocks the renal benefits of ramipril in diabetic hypertensive rats. 182 92

1. Streptozotocin diabetes was induced in Wistar-Kyoto rats fed a 50% protein diet. Animals were randomized to receive either the ACE inhibitor ramipril, 1 mg/L in drinking water (n = 7), or no treatment (n = 7) and were studied for 6 months. Blood glucose, body weight and glomerular filtration rate (GFR) were measured at 0, 1, 4, 8 and 16 weeks of diabetes and urinary albumin excretion was measured every 8 weeks. 2. In both groups, GFR increased significantly within 1 week of induction of diabetes (P less than 0.001) and thereafter remained stable. There was no difference in GFR between the treated and untreated groups. 3. Urinary albumin excretion increased progressively in both groups throughout the study. Ramipril treatment reduced albuminuria by approximately 50% at weeks 16 and 24 (P less than 0.01). 4. The amelioration of diabetic albuminuria by ACE inhibition, in the setting of high dietary protein intake, may have important implications for the treatment of human diabetic nephropathy.
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PMID:Ramipril reduces albuminuria in diabetic rats fed a high protein diet. 252 67

Ramipril is a second generation angiotensin converting enzyme (ACE) inhibitor. Like enalapril, it is a prodrug and is hydrolysed in vivo to release the active metabolite, ramiprilat, which has a long elimination half-life, permitting once-daily administration. The antihypertensive efficacy of ramipril has been confirmed in large-scale noncomparative studies conducted in general practice as well as in more rigorously controlled clinical trials. In the former, approximately 85% of patients with mild to moderate essential hypertension have responded successfully to treatment with ramipril 2.5 or 5 mg/day, while comparative trials indicate that the antihypertensive efficacy of the drug is equivalent to that of other established ACE inhibitors and the beta-adrenoceptor antagonist atenolol. As expected, the response rate to ramipril monotherapy is lower in patients with severe hypertension (around 40%), although the blood pressure lowering effect can be enhanced with the addition of a diuretic such as hydrochlorothiazide or piretanide. The antihypertensive efficacy of ramipril is maintained in patients with diabetes mellitus and preliminary data indicate that the drug has the beneficial effect of decreasing urinary albumin excretion in diabetic patients with nephropathy. Ramipril is superior to atenolol in causing regression of left ventricular hypertrophy, although the clinical significance of this effect per se remains to be established. The large-scale Acute Infarction Ramipril Efficacy (AIRE) study demonstrated that ramipril 5 or 10 mg/day significantly decreased the risk of all-cause mortality by 27% in patients with clinical evidence of heart failure after acute myocardial infarction, even if transient. The beneficial effect of ramipril was apparent by 30 days of treatment and appeared to be greatest in patients with more severe ventricular damage after infarction. Ramipril is well tolerated in general practice, with 5% or fewer patients discontinuing therapy because of drug intolerance. The data available suggest that ramipril shares a similar tolerability profile to that of other established ACE inhibitors. Thus, clinical data confirm ramipril as a useful alternative ACE inhibitor for the treatment of patients with mild to moderate hypertension, and indicate a beneficial effect of the drug in patients with clinical evidence of heart failure after acute myocardial infarction. It is also reasonable to assume that ramipril will be of value in the treatment of patients with more established heart failure or asymptomatic left ventricular dysfunction.
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PMID:Ramipril. An updated review of its therapeutic use in essential hypertension and heart failure. 777 15

This study investigated the protective effect of the angiotensin converting enzyme inhibitor, ramipril, on endothelium-dependent responses in arteries from control (CON) and streptozotocin-induced (STZ) diabetic rats. Three hypotheses were tested: 1) there is an endothelium-dependent component to the increased alpha-adrenergic responsiveness characteristic of diabetes; 2) endothelium-dependent, acetylcholine-induced relaxation is attenuated in aorta from diabetic rats; and 3) ramipril (3 mg/kg daily in the food, 12-15 weeks) will prevent functional vascular changes in diabetic rats. Vascular function was assessed in aortic rings using standard muscle bath procedures for measurement of isometric force. Sensitivity to phenylephrine was increased in aortic rings from diabetic compared to control values [pD2 values (-log ED50): CON = 6.22 +/- 0.12, STZ = 7.54 +/- 0.11), and removal of the endothelium (-Endo) increased phenylephrine sensitivity (CON-Endo = 7.40 +/- 0.11, STZ-Endo = 8.32 +/- 0.18). The magnitude of the shift in responsiveness following endothelium removal was greatest in control rats. Ramipril treatment (Ram) partially normalized phenylephrine responsiveness in intact (STZ + Ram = 6.55 +/- 0.11) and denuded (STZ-Endo + Ram = 7.75 +/- 0.10) vessels. Vasodilatation to acetylcholine and nitroglycerin was not altered in diabetic rats nor was it affected by ramipril treatment. Diabetes increases contractile sensitivity to phenylephrine but not to vasodilators and chronic ramipril treatment prevents this increase in contractile sensitivity. Ramipril treatment did not alter the hyperglycaemic condition induced by streptozotocin. The changes in phenylephrine sensitivity appear to involve an endothelial and a smooth muscle component.
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PMID:Ramipril prevents hypersensitivity to phenylephrine in aorta from streptozotocin-induced diabetic rats. 795 36

Ramipril blocks the conversion of angiotensin I to II. The literature indicates that diabetes is often associated with mild impairment of learning and memory. The study reports the effects of ramipril on memory retention in diabetic and non-diabetic mice. Mice were made diabetic by an injection of streptozocin. After overt signs of diabetes were present, diabetic or vehicle-treated mice were partially trained on a footshock active avoidance task. Immediately after training, ramipril (0.5-1.5 mg/kg s.c.) was administered and retention was tested by continuing training one week later until mice avoided footshock on five out of six trails. The results indicate that ramipril enhanced retention of both diabetic and control mice but it required about 5 times as much ramipril in diabetic as control mice to achieve the same effect on retention. Increased sensitivity to angiotensin II may play a role in cognitive impairment in diabetes.
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PMID:Dose-response differences in the ability of ramipril to improve retention in diabetic mice. 824 47

The role of angiotensin-converting enzyme (ACE) inhibition with ramipril on mesenteric vascular hypertrophy and urinary albumin excretion was explored in a normotensive model of experimental diabetes. Serial measurements of albuminuria were performed in Sprague-Dawley control, diabetic rats, and diabetic rats treated with ramipril. Over 24 weeks, urinary albumin excretion showed a continuous rise in the untreated diabetic rats. Ramipril prevented the increase in albuminuria over the whole study period. After 6 months, animals were perfused with glutaraldehyde and sacrificed for measurement of mesenteric vessel wall/lumen ratio and kidney weight. Diabetes was associated with increased mesenteric wall/lumen ratio and kidney weight. ACE inhibition, despite no effect on glycemic control, attenuated mesenteric vascular hypertrophy but did not decrease kidney weight. In addition to the well-described renoprotective effects of ACE inhibition in diabetes, this class of agents may have a favorable effect on diabetic vascular disease.
J Diabetes Complications
PMID:Diabetic vascular hypertrophy and albuminuria: effect of angiotensin converting enzyme inhibition. 857 56

Atherosclerotic cardiovascular disease remains a major cause of mortality and morbidity in most developed countries. Experimental and clinical evidence suggests that angiotensin-converting enzyme inhibitors and vitamin E therapy may retard the atherosclerotic process; however, definitive proof in humans is lacking. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) is designed to assess the effects of ramipril--an angiotensin-converting enzyme inhibitor, at 2 doses: 2.5 mg daily (which has little effect on lowering blood pressure) and 10 mg daily--and the antioxidant vitamin E, 400 IU daily, on atherosclerosis progression in 732 patients using a factorial 3 x 2 study design. High-risk patients with a documented history of significant cardiovascular disease or with diabetes and additional risk factors were enrolled and will be followed for 4 years. The extent and progression of atherosclerosis are assessed noninvasively by B-mode carotid ultrasonography. The SECURE trial is a substudy of the larger Heart Outcomes Prevention Evaluation (HOPE) study of 9,541 high-risk patients evaluating the effects of ramipril and vitamin E on major cardiovascular events (cardiovascular death, myocardial infarction, and stroke). The 2 studies are complementary. Whereas HOPE is expected to provide information on major clinical outcomes, SECURE will shed light on the mechanisms by which these effects may be mediated.
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PMID:Study design and baseline characteristics of the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E: SECURE. 888 65

The kallikrein-kinin system (KKS) has been postulated to play a role in modulation of hemodynamic function in diabetes and to contribute to the hemodynamic effects of angiotensin-converting enzyme inhibition (CEI). To further explore the KKS and its interactions with the renin-angiotensin system (RAS), studies were conducted in nondiabetic control rats and in moderately hyperglycemic diabetic rats. In protocol 1, control and diabetic rats were studied before and after administration of one of two dissimilar B2 kinin receptor antagonists (BK2As), or vehicle. At a low dose (0.5 microg x kg-1 x min-1), the first generation antagonist D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin significantly reduced the glomerular filtration rate (GFR) and renal plasma flow rate in diabetic rats, despite variable effectiveness in blocking the hypotensive response to injected bradykinin. However, a similar hemodynamic effect occurred in nondiabetic rats, suggesting that the observed effect was not specific to diabetes. Higher doses (20 microg bolus, then 1 microg x kg-1 x min-1 infusion) did not affect hemodynamics in either group, perhaps because of partial agonist effect. The second BK2A tested was the newer compound, icatibant (Hoe 140; D-Arg,[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin). Hoe 140 consistently blocked the vasodepressor action of injected bradykinin, but had no effect on systemic or renal hemodynamics in either control or diabetic rats. In protocol 2, control and diabetic rats were pretreated with the CEI ramipril for 1-2 weeks, after which renal function was studied before and after Hoe 140 (0.1 mg s.c. and i.v.) or vehicle. CEI lowered blood pressure in both groups. Hoe 140 did not affect renal function in control rats, but in diabetic rats pretreated with ramipril, it induced a modest but significant decline in GFR. Ramipril induced the predicted changes in the systemic and intrarenal RAS, while acute BK2A had no consistent effect on RAS parameters. These studies suggest that the endogenous KKS has only a minor role in modulation of renal hemodynamics in the euvolemic diabetic rat, in the absence of KKS stimulation by CEI. However, angiotensin-converting enzyme is also kininase II, which serves to increase endogenous kinin activity. The increased kinin activity resulting from CEI treatment may participate, to a modest degree, in hemodynamic regulation of the diabetic kidney.
Diabetes 1997 Jan
PMID:Interactions of the kallikrein-kinin and renin-angiotensin systems in experimental diabetes. 897 Oct 89

20 patients with essential hypertension and diabetes mellitus (DM) type II were given Capoten (100-125 mg/day for 6 weeks) followed in a 2-week interval after its course termination by ramipril (10.0-12.5 mg/day). 50% of patients were sensitive to Capoten, 50% were resistance: 35 and 40% to ramipril, respectively. Ramipril was discontinued because of toxicity in 25% of patients. Hypotensive effects of ramipril were weaker than Capoten, though the former drug appeared more potent in lowering of peripheral vascular resistance at rest and at reactive hyperemia. Vasodilatation did not differ much.
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PMID:[A comparison of the effect of Capoten (captopril) and ramipril on the circadian profile of the arterial pressure and peripheral hemodynamics in patients with hypertension combined with diabetes mellitus]. 908 6

1. In the present study the role of angiotensin II (AngII) in the development of cardiac hypertrophy in diabetes combined with hypertension was investigated. 2. Diabetes was induced in 8-week-old male spontaneously hypertensive rats (SHR) by intravenous injection of streptozotocin (45 mg/kg bodyweight). Diabetic SHR were treated with the angiotensin-converting enzyme (ACE) inhibitor ramipril at a dose of 0.4 mg/kg per day. 3. Twelve weeks following the onset of diabetes, hearts were arrested in diastole and were perfusion-fixed. The right ventricle and left ventricle plus septum were weighted and the volume of the ventricular walls was determined using the Cavalieri principle. 4. Induction of diabetes in SHR led to a significant reduction in bodyweight compared with non-diabetic control SHR and this was not affected by ramipril treatment. The development of hypertension was not as great in diabetic SHR compared with controls, such that at 12 weeks following the onset of diabetes systolic blood pressure (SBP) averaged 191 +/- 3 and 230 +/- 4 mmHg in diabetic SHR and controls, respectively. Ramipril treatment significantly lowered SBP in diabetic SHR. 5. The left ventricle plus septum volume:bodyweight ratio (LV vol:BW) was significantly higher in diabetic SHR compared with controls (3.83 +/- 0.19 and 3.26 +/- 0.16 mm3/g, respectively). Ramipril treatment did not affect growth of the left ventricle in diabetic SHR with the LV vol:BW ratio averaging 3.95 +/- 0.14 mm3/g. Similar trends on growth were observed in the right ventricle. 6. In conclusion, the development of cardiac hypertrophy in diabetic SHR appears to occur by mechanisms independent of AngII and the elevation of blood pressure.
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PMID:Cardiac hypertrophy in diabetic spontaneously hypertensive rats: role of angiotensin II? 917 55


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