Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of patients with severe heart failure by ACE inhibition is often limited by worsening of renal function. To evaluate whether trandolapril, a potent lipophilic ACE inhibitor, affects renal function in severe heart failure, we studied 12 patients with severe heart failure treated with only diuretics and digoxin. Patients received increasing oral dosages of trandolapril (0, 1, and 2 mg) on 3 consecutive days (A). Patients were then discharged on 2 mg trandolapril bid and re-evaluated 8 weeks later (B). Mean arterial and pulmonary wedge pressures decreased by maximal 14% and 43%, and stroke volume and work indexes increased by 24% and 20% at A and similarly at B (11, 45, and 25 ns and 33%, respectively). In contrast, heart rate, systemic resistance, pulmonary artery pressure, and cardiac index decreased by 6%, 23%, 29%, and 17%, respectively, at only A. Renal blood flow improved by approximately 40% both at A and B. In contrast, the glomerular filtration rate decreased by 25% at only B, whereas serum creatinine, creatinine clearance, and urine osmolality were unaffected during the study. Norepinephrine, angiotensin II, and aldosterone levels decreased by approximately 30%, 60%, and 65%, respectively, at both A and B. Renin levels increased by 136% at A and remained elevated at B. Thus, whereas the initial systemic vasodilating and inotropic effects did not persist, long-term trandolapril results in sustained neurohormonal modulation, reduced preload, and improved organ perfusion, indicated by a persistent increase in renal blood flow and preservation of renal function in severe heart failure.
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PMID:Renal hemodynamic effects in patients with moderate to severe heart failure during chronic treatment with trandolapril. 982 86

Endothelins (ET) are 21-aminoacid peptides produced ubiquitously, which were discovered originally as endothelial products. These peptides may play important roles in cardiovascular physiology and pathophysiology. As the pathophysiologic roles of endothelins in cardiovascular disease become increasingly apparent, the potential therapeutic use of endothelin antagonists or endothelin converting enzyme inhibitors is recognized. The main endothelin produced by the endothelium is ET-1. Endothelin-1 is overexpressed in the vascular wall of salt-dependent models of hypertension, such as DOCA-salt hypertensive rats, DOCA-salt-treated spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats, and in stroke-prone SHR, angiotensin II-infused rats and 1-kidney 1 clip Goldblatt hypertensive rats, but not in SHR, 2-K 1C hypertensive rats or L-NAME-treated rats. The vasoconstrictor effect of ET-1 may contribute to blood pressure elevation and its growth-promoting action to vascular hypertrophy in the hypertensive models which overexpress ET-1 in blood vessels. In rats without generalized activation of the endothelin system, expression of ET-1 is often enhanced in coronary arteries, which suggests a role for ET-1 in myocardial ischemia in hypertension. In rats overexpressing ET-1, ETA/B and ETA-selective antagonists lowered blood pressure slightly, and significantly reduced vascular growth, particularly of small arteries, suggesting that ET-1 has a direct effect on growth. Protection from renal injury and from stroke has also been demonstrated in hypertensive rats treated with endothelin antagonists. In normotensive human subjects endothelin-dependent tone can be shown in the forearm. In a study of mild hypertensive patients, the ETA/B antagonist bosentan reduced blood pressure similarly to an ACE inhibitor. Moderate to severe hypertensive patients presented enhanced expression of ET-1 mRNA in the endothelium of subcutaneous resistance arteries. In blacks with familial hypertension increased plasma levels of endothelin have been found. Thus, ET-1 may play a role in some experimental hypertensive models and in human hypertension. In summary, endothelial ET-1 may be overexpressed in the more severe forms of hypertension, and in certain special populations which may respond particularly well to endothelin antagonism. Endothelin antagonists may prove to be effective disease-modifying agents if in future clinical trials they are shown clinically to blunt vascular growth and endothelial dysfunction, reduce stroke and exert the cardioprotective and renal protective effects already reported in experimental hypertension. These agents could contribute to reduce the long-term complications of hypertension, which remains to be demonstrated in humans.
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PMID:Endothelin: role in hypertension. 983 May 7

Most antihypertensives have advantages and disadvantages. The ideal antihypertensive drug should be effective in lowering blood pressure, well tolerated, safe in the long term, and easy to use. Ideally, it should be relatively inexpensive. Most importantly it should reduce the risk of the adverse effects of high blood pressure, such as myocardial infarction, sudden death, stroke, heart failure, renal damage, and retinal changes. Most antihypertensive drugs effectively reduce blood pressure, are available as once daily preparations, and are safe long-term. Unfortunately, most antihypertensive drugs cause adverse effects in some patients and for few drugs is there good evidence that they protect the heart, the brain, the kidney, and the eye? Reducing the effects of Angiotensin II (using an ACE inhibitor) has been shown to reduce the incidence of coronary events, sudden death, heart failure, renal damage, and fundal changes. AT1 blocking drugs offer the same pharmacological advantages but also very good tolerability, in particular no cough. Therefore, they have the potential to meet all the criteria for an ideal antihypertensive drug.
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PMID:Therapeutic advantages of AT1 blockers in hypertension. 983 62

Hypertension is a major risk factor for premature death. Large outcome studies have demonstrated reduced morbidity and mortality associated with antihypertensive therapy in mixed patient populations, but data on morbidity and mortality in defined ethnic groups are lacking. Management of cardiovascular risk factors, which frequently coexist with hypertension, presents a logical management strategy in these patients. Indo-Asian patients are particularly prone to insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM), which are associated in turn with potentially atherogenic lipid profiles and poor cardiovascular outcomes. Diuretics and beta-adrenoceptor blockers exert theoretically adverse effects on lipid profiles and should be used with caution in Indo-Asian patients at risk of developing NIDDM. Hypertensive African-Caribbean patients are at increased risk of stroke and tend to suffer greater target organ damage, including renal dysfunction and cardiac hypertrophy. Hypertension in African-Caribbean patients is less sensitive to beta-adrenoceptor blockade or ACE inhibition than in white patients. Selective alpha 1-adrenoceptor antagonists and calcium channel blockers are equally effective antihypertensive agents in all races. While calcium channel blockers are metabolically neutral, alpha 1-adrenoceptor blockers promote a potentially less atherogenic lipid profile. Further study of the effects of antihypertensive treatment on morbidity and mortality in ethnic groups is required, particularly in Indo-Asian patients.
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PMID:Blood pressure control and cardiovascular risk in patients of Indo-Asian and African-Caribbean descent. 989 75

Important intervention trials performed during the last decades and years are presented and critically reviewed. These long-term studies with hard end points have demonstrated positive results for four different antihypertensive classes: diuretics, beta blockers, calcium channel blockers and ACE inhibitors. The major issue is the prevention of hypertensive complications such as myocardial infarction, heart failure or stroke. For achieving this primary goal blood pressure reduction--or ideally normalization--is of decisive importance. As recommended by the Deutsche Hochdruckliga (German "Hypertension League") specific and individualized treatment of hypertension should consider target organ protecting effects of the various antihypertensive agents. In many cases combination therapy will be necessary to control hypertension (blood pressure target < 140/90 mmHg).
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PMID:[Study on intervention in arterial hypertension. Recommendations by experts and practical antihypertensive therapy. German Hypertension League]. 1009 98

Morbidity and mortality in diabetes are caused mainly by its vascular complications, both in the microcirculation and in the large vessels. Diabetic nephropathy and retinopathy are the clinical hallmarks of microangiopathy, which may lead to end-stage renal failure and blindness. The cardiovascular complications in diabetes consist mainly of an accelerated form of atherosclerosis. Systemic hypertension is an early and frequent phenomenon. Nocturnal hypertension is also more frequent in people with diabetes compared with the nondiabetic population. Capillary hypertension has been demonstrated in type 1 diabetic patients. Poor metabolic control may induce elevation in blood pressure, but data are conflicting. The prevalence of white-coat hypertension in the diabetic population is comparable with that in the nondiabetic population. Prospective observational studies in type 1 and type 2 patients have revealed that abnormally increased urinary albumin excretion and other potentially modifiable risk factors--such as hypertension, smoking, poor metabolic control, and social class--predict increased all-cause mortality and cardiovascular mortality. Arterial hypertension is a risk factor in the initiation and progression of diabetic micro- and macroangiopathy. Diabetes, hypertension, and smoking are the three most important risk factors for fatal and nonfatal stroke. A randomized, double-blind, parallel study has revealed that the 5-year major cardiovascular disease rate was lowered by 34% for antihypertensive treatment compared with placebo. Furthermore, the study found a trend for lower all-cause mortality for low-dose antihypertensive-treated diabetic patients. Effective blood pressure reduction with ACE inhibitors and/or non-ACE inhibitors, frequently in combination with diuretics, reduces albuminuria, delays the progression of nephropathy, postpones end-stage renal failure, and improves survival in diabetic nephropathy.
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PMID:Diabetic hypertensive patients. Is this a group in need of particular care and attention? 1009 4

In Eisenmenger's syndrome a central left-to-right shunt in the heart, a congenital anomaly, leads to pulmonary hypertension which subsequently causes the shunt to be reversed. The hypoxaemia resulting from a right-to-left shunt is compensated by an increase of the haemoglobin concentration due to a rise of the haematocrit. In adult patients not operated (adequately), the symptoms are the consequence of the erythrocytaemia and an increased haemorrhagic diathesis. In the long run heart failure develops. Phlebotomy is indicated for patients with haematocrits higher than 0.65 with signs of hyperviscosity and is also advised before non-cardiac surgery to improve coagulation parameters. Phlebotomy should be performed slowly (500 ml in 30-45 min) with simultaneous volume replacement. Excessive phlebotomy causes iron deficiency and spherocytosis which increase viscosity as well as the risk of CVA. Treatment consists of iron supplementation. Anticoagulation is indicated only in case of atrial fibrillation or mechanical valves. The use of acetylsalicylacid or NSAIDs is relatively contraindicated, because of abnormal haemostasis in these patients. During treatment with ACE inhibitors and other vasodilators, hypovolaemia should be avoided, because at a lower systemic blood pressure the right-to-left shunt increases and a potentially fatal cyanosis may occur.
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PMID:[Eisenmenger syndrome in adults]. 1032 Dec 57

Patients with type 2 diabetes mellitus often develop micro- and macrovascular complications. In 25% of them, complications are already present at the time of diagnosis. The principal objective of the United Kingdom prospective diabetes study was to determine if good blood glucose control and adequate treatment of hypertension in patients with type 2 diabetes mellitus can prevent development of diabetes-related complications. The question was also studied if they way in which this blood glucose control was achieved and the way of treating the blood pressure affected the prognosis. Blood glucose control was found to reduce the incidence of--especially--microvascular complications. Oral hypoglycaemic agents and insulin both play an important part in achieving good control. Treatment with metformin reduced mortality due to cardiovascular disease in obese patients. Strict control of the blood pressure reduced development of micro- and macrovascular complications; the mortality from diabetes-related disorders and the numbers of patients suffering a stroke or heart failure. Non of the antihypertensive drugs used (an ACE inhibitor and a beta-blocking agent) offered any advantages over the other.
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PMID:[Glycemic regulation and management of essential hypertension in diabetics with type 2 diabetes mellitus; the 'United Kingdom prospective diabetes study' of diabetic complications]. 1038 31

Diabetes mellitus and hypertension is often associated, but with a different type of development in type 1 and type 2 diabetes. Type 1 diabetes, renal disease, starting with microalbuminuria, is associated with increasing blood pressure or hypertension, whereas the patient without renal disease is most often normotensive. Poor metabolic control is a predictor of microalbuminuria or incipient nephropathy, but with microalbuminuria hypertension is an important risk factor for progression along with poor glycemic control. The same is the case for overt renal disease, and metabolic control is important in all stages of renal disease in type 1 diabetes. It has also been shown that good metabolic control as well as antihypertensive treatment, especially with ACE-inhibitors, often combined with other agents is quite effective in preventing progression in renal disease in all its stages. In type 2 diabetes, blood pressure elevation is often found as early as at the actual diagnosis, and blood pressure significantly increases according to the degree of albuminuria, normo-microalbuminuria and clinical proteinuria (macroalbuminuria). Elevated blood pressure is an important risk for renal disease but more importantly so also for cardiovascular disease. Several studies document that antihypertensive treatment in particular with ACE-inhibitors is important in preventing microalbuminuria, in treating microalbuminuria and thus preventing progression, also in overt renal disease. Near-normalization of blood pressure is vital. Regarding cardiovascular disease, a series of studies now document that antihypertensive treatment with various antihypertensive agents is able to significantly reduce a number of major cardiovascular complications in diabetes, such as cardiac disease, stroke, and also microvacular disease, including retinopathy. Several studies show that antihypertensive treatment should be started at a level higher than 140-150/90. The blood pressure to be achieved during treatment is probably around 140/85 mmHg or even 130/80 mmHg as a pragmatic goal. However, there is no sign of a J-shaped curve in any of the studies, and therefore even lower blood pressure could be advantageous. Even mortality, at least from diabetes-related causes can be effected by antihypertensive treatment. With more advanced renal disease, normalization of blood pressure is increasingly difficult, especially systolic blood pressure, and therefore it is recommendable to screen patients much earlier on with focus on blood pressure recordings and measurements of albuminuria, including microalbuminuria, and to treat early.
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PMID:Drug treatment for hypertensive patients in special situations: diabetes and hypertension. 1042 11

The aim of the study was to investigate the influence of long-term ACE inhibition with ramipril on myocardial hypertrophy and its molecular background in spontaneously hypertensive stroke-prone rats (SHR-SP). Therefore, 1-month-old pre-hypertensive SHR-SP were randomized into three groups and exposed lifelong via drinking water to 1 mg/kg/day ramipril (anti-hypertensive dose, RHI), 10 micrograms/kg/day ramipril (non-anti-hypertensive dose, RLO) or placebo. After 15 months cardiac tissue was collected from ten rats each for immunohistochemistry and Northern blot analysis of structural proteins, proteins of the extracellular matrix and several growth factors. Results showed that RHI, but not RLO, treatment prevented development of myocyte hypertrophy (ANP). Furthermore, unlike placebo-treated rats, the ramipril-treated animals had no evidence of degeneration and loss of structural proteins (alpha -actinin), inflammatory infiltrates (CD45) and deposition of extracellular matrix proteins (collagen, fibronectin, vimentin). Only in RHI-treated animals, mRNA levels for TGF- beta(1)as well as of collagen alpha(1)(I) and fibronectin were downregulated compared to placebo-treated animals. In contrast, VEGF mRNA levels increased significantly in both groups of ramipril-treated animals v. placebo-treated SHR-SP. Thus, the reported life prolonging effect of high doses of ramipril which is associated with prevention of hypertension and hypertrophy is accompanied by prevention of the development of necrosis and fibrosis. The role of VEGF, however, seems to be independent of this effect.
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PMID:Effect of long-term ACE inhibition on myocardial tissue in hypertensive stroke-prone rats. 1042 43


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