Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, we have shown that chronic administration of N-Nitro-L-Arginine Methyl Ester (L-NAME, an inhibitor of nitric oxide synthase) precipitates stroke in stroke-prone spontaneously hypertensive rats (SHRSP). Angiotensin receptor antagonist (L-158,809) was shown to delay the onset of such stroke. In the present study, five groups of 4-week-old SHRSP were used. Three groups of SHRSP were made diabetic using streptozotocin (100 mg/kg i.p.). SHRSP from groups I (non-diabetic) and III (diabetic) chronically received L-NAME(0.5 g/L) and L-158,809 (20 mg/L) in saline to drink. Diabetic SHRSP (group C) received only saline to drink. SHRSP groups I and III developed stroke in 10+/-2 and 11+/-2 days. Average stroke-free period in groups II and IV was 18+/-2 and 29+/-2 days, respectively. Protective effect of streptozotocin-induced diabetes disappeared when SHRSP drinking L-NAME and L-158,809, also received subcutaneous injections of insulin. Present data suggest that experimental diabetes delays the onset of L-NAME-induced stroke in SHRSP and this protection is seen in the absence of renin-angiotensin system.
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PMID:Effect of experimental diabetes on the protection by angiotensin blockers on nitric oxide deficient stroke in stroke-prone spontaneously hypertensive rats. 1005 40

Angiotensin converting enzyme inhibitors (ACE-I) are a mainstay for the treatment of heart failure, and of diabetic microalbuminuria. Recently ACE-I have been found to decrease plasma levels of circulating vascular cell adhesion molecule-1 (cVCAM-1) in patients with congestive heart failure. As increased cVCAM-1 levels are pathognomonic for diabetics with microangiopathy, we investigated the effects of ACE-I on plasma levels of cVCAM-1, intercellular adhesion molecule (cICAM-1), and cE-selectin in microalbuminuric diabetics. In addition, the effects of ACE-I on plasma levels of plasminogen activator inhibitor (PAI-1) and of tissue plasminogen activator (TPA) were studied. Fosinopril (10 mg/day) was administered over 12 weeks to 11 microalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM). As expected, baseline plasma concentrations of cE-selectin, cICAM-1, and cVCAM-1 were markedly higher in patients than in healthy control subjects (n = 82; P < .001). PAI-1 levels in NIDDM were similar to those in control subjects, whereas TPA levels were about 25% lower in patients than in control subjects (P = .013). Serum levels of cVCAM-1 decreased by -19% (CI: -25% to -13%) after treatment with fosinopril (P = .003) and were no longer different from those of the control group. In contrast, plasma levels of cE-selectin, cICAM-1, PAI-1, and TPA were unaffected. As expected microalbuminuria decreased by -44% (CI: -65 to -22; P = .004). In conclusion, fosinopril lowered cVCAM-1 levels along with microalbuminuria in NIDDM. This may represent a novel mechanism of action of ACE-I in diabetes-associated endothelial dysfunction. Whether decreased VCAM-1 expression is responsible for the observed reduction in microalbuminuria, deserves further investigation.
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PMID:Fosinopril decreases levels of soluble vascular cell adhesion molecule-1 in borderline hypertensive type II diabetic patients with microalbuminuria. 1009 Mar 51

Renal failure is a common long-term complication of diabetes mellitus. Stages of diabetic nephropathy have been described that characterize its clinical course. Diabetic nephropathy develops secondary to long-standing hyperglycemia and hemodynamic changes that damage the glomerulus. Therapy that focuses on the control of glomerular pressures and systemic hypertension can slow the progression of proteinuria and deterioration of renal function. Angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers have been demonstrated to be effective in the management of diabetic nephropathy. A systematic approach to the patient with diabetes with annual screening for proteinuria will help identify those individuals early in the course of disease when proper therapy may be most helpful.
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PMID:Approach to the treatment of diabetic nephropathy. 1016 75

Approximately 50 million people have hypertension. Many agents with differing efficacy, side effects, dosing schedules, and costs are available to treat hypertension. Joint National Committee (JNC) guidelines attempt to simplify this decision by recommending specific agents based on special considerations such as comorbidities. The objective of this study was to survey primary care physicians' antihypertensive prescribing practices and their treatment recommendations for patients with comorbidities. A direct mail survey was sent to a national random sample of 500 office-based primary care internists, family practitioners, and general practitioners. There were no significant differences between initial treatment recommendations at the time of the survey and those recommended before the survey. However, there were several therapeutic classes whose reported utilization for specific comorbidities significantly changed over 18 months. Angiotensin converting enzyme (ACE) inhibitors reportedly increased in patients with congestive heart failure and diabetes. In addition, the reported use of selective beta-blockers increased for patients with a history of myocardial infarction. Physicians did not follow JNC recommendations when initiating treatment in black patients, older patients, or those with mild renal failure. Younger physicians were more likely than older physicians to select agents consistent with guideline recommendations. Physicians did not adhere to JNC guidelines when initiating treatment in patients with comorbidities; however, more physicians are prescribing recommended agents today as compared to 18 months ago. Younger physicians were more likely to prescribe agents consistent with the guidelines. More direct efforts are needed to ensure awareness and compliance with these guidelines.
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PMID:Treatment of hypertension in patients with comorbidities: results from the study of hypertensive prescribing practices (SHyPP). 1023 92

Angiotensin II (AII) acts by 2 types of receptors: the ATI receptor which mediates its actions on vasoconstriction, renin (inhibition) and aldosterone (stimulation) secretions, cellular proliferation and angiogenesis and the non-AT1 (often called AT2) receptors. Mainly expressed in the embryon these latter may favor cellular differentiation and recruitment of collateral circulation. Angiotensin converting enzyme inhibitors (ACEI) decrease the synthesis of All and therefore the stimulation of both receptor types whereas AT1-receptor antagonists (AT1RA) block only the stimulation of these latter and increase the stimulation of AT2 receptor since they increase the production of All secondarily to the inhibition of the feedback of renin secretion by All. Experimentally ACEI and AT1RA decrease angiogenesis and cellular proliferation and favor cellular differentiation which could explain the protective effect of ACEI against cancer suggested recently in a Scotish study. Despite of their common suppressive effect on angiogenesis AT1RA may better than ACEI protect against ischemic events specially the cerebral ones because they favor the rapid recruitment of collateral circulation. This has been demonstrated for losartan in case of abrupt ligation of the carotid in the gerbil since its previous administration protects against fatal cerebral ischemia whereas its previous administration with enalapril abolishes this protection. These data may explain why, in the CAPP trial, captopril which has prevented more effectively diabetes occurrence could not be proved superior to diuretics and/or betablocker in the prevention of myocardial infarction and specially of strokes for which exist on the contrary a suspicion of a lower protection. Therefore a comparative trial between AT1RA and ACEI in the prevention of stroke recurrence should appear as a priority for Public Health and Pharmaceutical Industry Authorities.
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PMID:[Duality of angiotensin II receptors and risk for stroke and cancer: what is the connection?]. 1036 Jan 91

We evaluated the effects of angiotensin II and an angiotensin-converting enzyme inhibitor (cilazapril) on nerve blood flow (NBF) and electrophysiology in control and diabetic rats. When applied locally to the sciatic nerve, the dose-response curve of angiotensin II was more potent in experimental diabetic neuropathy (EDN) than control rats. No difference existed in plasma angiotensin II levels between EDN and controls. The rats were given typical rat pellets or pellets treated with 10 mg/kg per day cilazapril for 4 weeks. Diabetes caused a significant reduction in NBF, nerve conduction velocity, and compound muscle action potential (CMAP) amplitudes. NBF was significantly increased in diabetic rats supplemented with cilazapril diet, and nerve conduction velocity and amplitudes of the CMAP were also improved after 4 weeks on this diet. Direct application 10(-3) mol/L cilazapril on sciatic nerve did not increase NBF in normal and EDN rats. We topically applied the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine, on sciatic nerve and observed reduced inhibition of NBF in EDN, which was correctable with a cilazapril diet. These results suggest that diabetic neuropathy may have an increasing vasopressor action with angiotensin II and this is likely to be the mechanism of NOS inhibition. Angiotensin II-converting enzyme inhibitors may have potential in the treatment of diabetic neuropathy.
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PMID:Altered vasoreactivity to angiotensin II in experimental diabetic neuropathy: role of nitric oxide. 1039 11

Angiotensin converting enzyme (ACE) inhibitors have been shown to reduce the risk of death, worsening heart failure and recurrent infarction in patients with left ventricular dysfunction and heart failure. They have also been shown to reduce mortality in the acute phase of myocardial infarction. They have been demonstrated to reduce major vascular events and progression of renal disease in diabetes with hypertension, compared to placebo and to calcium channel blockers. Current trials are evaluating their role in preventing major vascular events in patients with coronary artery disease, strokes and Type II diabetes who are normotensive.
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PMID:Summary of randomized trials of angiotensin converting enzyme inhibitors. 1042 6

In a hospital cohort study, we examined whether or not ACE (Angiotensin-I converting enzyme) and AGT (Angiotensinogen) gene polymorphisms were associated with the development of nephropathy in long-term Japanese insulin-dependent diabetes mellitus (IDDM) patients with or without proliferative retinopathy, and whether or not the polymorphisms were associated with an arteriosclerotic family history in first degree relatives of the patients. A total of 201 patients with IDDM for more than 10 years and 159 patients with IDDM for more than 15 years were randomly selected in our hospital. All patients received uniform diabetes management and were divided into three groups, no nephropathy, incipient nephropathy and clinical nephropathy groups. There were no differences in clinical characteristics excluding urinary albumin to creatinine ratio and systolic blood pressure between the three groups. ACE I/D polymorphism was related to plasma ACE activity, but there were no associations between ACE I/D polymorphism and the development of diabetic nephropathy, nor was renal deterioration observed in patients with proliferative retinopathy even in those with a history of diabetes for more than 15 years. The AGT polymorphism did not have an additive effect on the association between ACE polymorphism and the development of diabetic nephropathy in patients with or without retinopathy. Development of diabetic nephropathy in the patients with or without proliferative retinopathy did not result in ACE or AGT polymorphisms. On the other hand, the ACE DD genotype was associated with a family history of ischemic heart disease in first degree relatives (X2 score = 9.04, P < 0.05). ACE and AGT gene polymorphisms may not play a role in the protective or accelerative effect against the development of diabetic nephropathy in the patients with or without proliferative retinopathy, but ACE gene polymorphism might be related to an arteriosclerotic family history in Japanese IDDM patients.
Diabetes Res Clin Pract 1999 Aug
PMID:Genetic polymorphism of renin-angiotensin system is not associated with diabetic vascular complications in Japanese subjects with long-term insulin dependent diabetes mellitus. 1049 84

Hypertension (HT) is a common disease in elderly. It has different pathophysiologic, clinical and therapeutic implications in this age group. Due to loss of arterial wall elasticity with age, major vessels including aorta become stiff and less distensible. As age advances, these stiff vessels also lose beta adrenergic responsiveness with unchanged alpha adrenergic responsiveness. These together raise peripheral vascular resistance and aortic impedance which needs a powerful systolic ejection of left ventricle to maintain cardiac output. Result is rise in systolic blood pressure (SBP) and increase in left ventricular (LV) mass with compromised cardiac output and renal blood flow. Participation of renin-angiotensin system and kidney in HT pathogenesis in elderly are minimum. Diagnosis of HT in elderly is made if SBP > 140 mm Hg and/or diastolic blood pressure (DBP) > 90 mm Hg or is taking antihypertensive medications. Isolated systolic hypertension (ISH) means SBP > 140 mm Hg with DBP < 90 mm Hg. Measurement of blood pressure (BP) is problematic, mainly due to pseudo HT, postural hypotension and white-coat HT. HT in absence of end organ changes suggest pseudo HT. Postural hypotension must be detected and treated. Systolodiastolic HT, carried over from middle age is the commonest type of HT in elderly. ISH is also common (10%). Atherosclerotic renovascular disease can cause secondary HT. Therapy is always needed in HT in elderly. Chance of coronary artery disease (CAD) and cerebrovascular accident (CVA) are quite high amongst elderly hypertensives. SBP is more dangerous than DBP. Benefits of therapy are more when compared to young. HT should be treated if SBP > 160 mm Hg and/or DBP > 90 mm Hg. ISH needs therapy if SBP > 160 mm Hg. The benefits of therapy becomes less after 80 years. Treatment goal should be to keep BP below 140/90 mm Hg. Therapy should be gradual and stepwise. Na-restriction should be modest. Diuretics (e.g., thiazide 25 mg/day) are the drug of choice unless contra-indicated. Beta blockers are inferior agents compared to diuretics unless angina or acute myocardial infarction (AMI) is present. Angiotensin converting enzyme (ACE) inhibitors are drug of choice only if congestive cardiac failure (CCF) and/or diabetes is present or other drugs are contra-indicated. Calcium entry blockers (CEB) are new but very good alternative to diuretics in elderly. Due to abnormal physiology, pharmacokinetics and drug interactions, side-effects are very common in elderly. They should be detected early and treated.
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PMID:Hypertension in elderly--an overview. 1065 9

Acute myocardial infarction (MI) is the leading cause of death around the globe. Advances in the field of cardiology have identified several effective treatments that have lead to decrease in mortality from this cause over the past 3 decades. The purpose of this article is to review the existing literature in regards to secondary prevention after acute MI. A search of MEDLINE through August of 1999 was carried out to identify any available publications on secondary prevention after MI. Evidence on the use of both pharmacological and nonpharmacological interventions that was shown to be effective in improving morbidity and mortality was sought. Recommendations for the treatment of patients with acute MI are made based on existing evidence. Betablockers, aspirin and lipid-lowering agents for patients with low density lipoprotein-cholesterol > 130 mg% should be used for all patients following a MI. Angiotensin converting enzyme inhibitors are indicated for patients with congestive heart failure and/or reduced left ventricular ejection fraction and are likely protective in most patients. Calcium channel blockers (Verapamil and Diltiazem) are indicated as second-line therapy for patients who have contraindications or are intolerant to betablockers. The routine prophylactic use of antiarrhythmic drugs to suppress ventricular ectopic beats should be avoided. Recommendations regarding diet, smoking cessation and achievement of ideal body weight should be an integral part of patient management. Referral for outpatient rehabilitation should also be strongly encouraged. Finally, adequate control of blood pressure and diabetes cannot be overemphasized. Adherence to these goals in patients with acute MI will lead to better long-term outcomes and reduction in cardiac death, recurrent MI, stroke, and need for coronary revascularization.
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PMID:Current concepts in secondary prevention after acute myocardial infarction. 1071 9


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