Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported that the in vitro enzymatic activity of exogenous renin, plasma renin reactivity (PRR), is increased in plasma of patients with chronic renal failure, possibly due to the deficiency of a renin inhibitor. To determine whether increases PRR is related to renal failure per se or to hyperlipidemia, PRR was measured in 10 control subjects, 10 patients with renal failure, and 10 hyperlipidemic patients with normal renal function. Compared to that in control subjects (52.6 ng angiotensin I generated per ml/h +/- 3.8 SE) PRR was increased (P < 0.05) in plasma of uremic patients (65.1 +/- 4.3) and hyperlipidemic patients (71.4 +/- 10.7). Renin substrate concentration did not differ among groups, and after denaturation of endogenous substrate by acidification of plasma, PRR was still increased. A "protein-free" extract of plasma from normal subjects inhibited renin, whereas little or no inhibition occurred with a comparable extract from uremic patients and hyperlipidemic patients. Thus, alterations in lipid metabolism may account for the increased enzymatic activity of renin in uremic plasma. Increased PRR may be related to the deficiency of a normally occurring renin inhibitor.
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PMID:Increased enzymatic activity of renin and hyperlipidemia. 700 15

A 34-year-old female complaining of numbness and weakness of the extremities was examined. Consanguineous marriage was contracted between mother and father. She was of short stature (149 cm), and her blood pressure was normal (118/60 mmHg). Her serum potassium concentration had decreased to a level between 2.5 and 3.2 mEq/L, and hypokalemic alkalosis was present. Potassium clearance had increased and urinary concentrating capacity was impaired. Plasma renin activity was high at 25 ng/ml/hr but plasma aldosterone concentration was normal. Hypertensive response to angiotensin II (50 ng/kg/min) was weak but improved to nearly the normal value after the administration of indomethacin for 17 days at a dose of 50 mg/day. A slight elevation in blood pressure was observed during the infusion of norepinephrine (250 ng/kg/min). A decrease in blood pressure was observed during the infusion of 1-sarcosine, 8-isoleucine angiotensin II (600 ng/kg/min) with concomitant increase of plasma renin activity. Twenty-four hour urinary excretion of prostaglandin E decreased somewhat (225 approximately 252 ng/day), and hyperplasia of the juxtaglomerular cells and increased JG index were demonstrated in the biopsy specimens of the right kidney. From the findings, the present case were diagnosed as Bartter's syndrome. Although mild enlargement of the sella turcica was found in skull x-ray films, no abnormalities in pituitary function were demonstrated. Other unusual complications, i.e. hyperlipidemia (type II, beta-dominant) and abnormal configuration of peripheral erythrocytes, were demonstrated. Phospholipid composition of the erythrocyte membrane was normal. The fluidity of plasma VLDL examined by electron spin resonance was increased. Hypokalemia and hyperreninemia were improved through the administration of indomethacin. However, because of headache as an adverse effect, further administration could not be accepted. The patient's complaints were resolved by the rectal application of indomethacin with oral administrations of spironolactone and triamterene. Changes in serum lipid levels did not occur with the above mentioned treatment. alpha-tocopheryl nicotinate lowered the levels of serum lipids and normalized the configuration of peripheral erythrocytes. But increased fluidity of plasma VLDL remained, and phospholipid composition of erythrocyte membrane was also unchanged. The relationship between the rare complications mentioned above and the pathophysiology of Bartter's syndrome is still obscure.
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PMID:[A case with Bartter's syndrome associated with type II hyperlipidemia, increased fluidity of plasma VLDL and abnormal configuration of peripheral erythrocytes (author's transl)]. 704 42

A high rate of cardiovascular death in renal patients, particularly patients with endstage renal failure, has not been well appreciated in the past. It is obvious that cardiovascular lesions are more severe than can be explained by the classical risk factors of elevated blood pressure and dyslipidemia. In renal failure, a number of pathomechanisms are operative which may be paradigms of more general relevance, e.g. activation of the renin and sympathetic system, inhibition of the vasoconstrictor NO system, left ventricular hypertrophy in excess of what is expected for high blood pressure. A paradox inverse relation between lipid concentrations and cardiovascular death, i.e. a protective effect of hyperlipidemia, in dialysed patients, presumably results from the confounding effect of malnutrition, high lipid levels being a substitute marker of adequate nutrition.
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PMID:Excess cardiovascular mortality in the uremic patient--what does it teach for other risk factors in the non-renal patient? 773 91

Proteolytic enzymes, lipase, kinins, and other active peptides liberated from the inflamed pancreas convert inflammation of the pancreas, a single-organ disease of the retroperitoneum, to a multisystem disease. Adult respiratory distress syndrome, in addition to being secondary to microvascular thrombosis, may be the result of active phospholipase A (lecithinase), which digests lecithin, a major component of surfactant. Myocardial depression and shock are suspected to be secondary to vasoactive peptides and a myocardial depressant factor. Coagulation abnormalities may range from scattered intravascular thrombosis to severe disseminated intravascular coagulation. Acute renal failure has been explained on the basis of hypovolemia and hypotension. The renin-angiotensin alterations in acute pancreatitis (AP) as mediators of renal failure need to be studied. Metabolic complications include hypocalcemia, hyperlipemia, hyperglycemia, hypoglycemia, and diabetic ketoacidosis, of which hypocalcemia has been long recognized as an indicator of poor prognosis. The pathogenesis of hypocalcemia is multifactorial and includes calcium-soap formation, hormonal imbalances (e.g., parathyroid hormone, calcitonin, glucagon), binding of calcium by free fatty acid-albumin complexes, and intracellular translocation of calcium. Subcutaneous fat necrosis, arthritis, and Purtscher's retinopathy are rare. The various prognostic criteria of AP and other associated laboratory abnormalities are manifestations of systemic effects. Early recognition and appropriated management of these complications have resulted in improved prognosis of severe AP.
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PMID:Acute pancreatitis: a multisystem disease. 804 85

After a brief synopsis of the classical antihypertensive drugs a survey is given of the newer therapeutics, such as calcium antagonists, ACE-inhibitors and alpha 1-adrenoceptor antagonists. Experimental drugs, such as imidazoline receptor agonists, renin inhibitors, angiotensin II receptor antagonists, alpha 2-adrenoceptor antagonists, potassium channel openers, ketanserin, endopeptidase inhibitors, and hybrid (multifactorial) drugs are discussed, with special attention for their modes of action. In spite of the ever increasing number of antihypertensive drugs and principles, the large scale of clinical evidence for a beneficial effect of long-term treatment (in particular with respect to protection against stroke) remains limited to diuretics and beta-blockers. In spite of this limitation it seems worthwhile to consider the newer antihypertensive drugs as well, especially for optimal treatment of the individual patient. The newer drugs may in particular offer special advantages in the presence of concomitant diseases, such as diabetes mellitus, hyperlipidaemia, angina pectoris or congestive heart failure.
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PMID:New avenues in antihypertensive drug treatment. 826 86

Patients who develop diabetic nephropathy, one of the leading causes of end-stage renal diseases in Western communities, have an increased red cell Li+/Na+ countertransport (CT). Li+/Na+ CT is a membrane function which exchanges intracellular Li for extracellular Na in vitro. High Li+/Na+ CT reflects abnormal kinetic properties of red cell membrane Na/H exchange. A widespread abnormality of Na/H exchange could play a major role in the pathogenesis of diabetic nephropathy as well as of cardiovascular diseases since Na/H exchange is involved in the regulation of cell pH and cell volume; in the cellular response to hormones, mitogens, and growth factors; and in the renal reabsorption of Na and bicarbonate. Li+/Na+ CT is under genetic control and raised in a subgroup of patients with essential hypertension. Among these patients, high Li+/Na+ CT is associated with increased glomerular filtration rate, filtration fraction, proximal fractional Na reabsorption, microalbuminuria, plasma renin activity, and kidney and cardiac volume. Increased Li+/Na+ CT is often associated with hyperlipidemia, hyperuricemia, reduced insulin sensitivity, and obesity. The whole of these observations may explain why patients with diabetes or essential hypertension and increased Li/Na CT are at risk of early renal and cardiac impairment.
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PMID:Red blood cell Li+/Na+ exchange in patients with diabetic nephropathy and essential hypertension: therapeutic implications. 851 86

During the last decade, our understanding of the role of nitric oxide for central renal functions has greatly been enhanced. We know now that nitric oxide is produced in renal arteries, macula densa, glomeruli, and tubules by different NO-synthases. Nitric oxide contributes to physiological regulation of renal blood flow, renal autoregulation, tubuloglomerular feedback, renin release, pressure natriuresis, and tubular function. The physiological role of nitric oxide can be modulated by a variety of pathophysiological influences, such as dyslipidemia, diabetes mellitus, hypertension, specific drugs, or radiocontrast agents. In this article, the possible interactions between nitric oxide and atherogenic lipoproteins with regard to important renal functions and development of glomerulosclerosis have been stressed. Atherogenic lipoproteins impair endothelium-dependent, nitric oxide-mediated dilations of renal arteries. The underlying mechanism involves formation of reactive oxygen species which inactivate nitric oxide. Lipoproteins induce formation of oxygen radicals not only in arteries, but also in glomeruli and juxtaglomerular cells, causing, e.g., stimulation of renin release. Although interactions between lipoprotein and nitric oxide take place at different levels, they finally may contribute to renovascular hypertension. Future studies will have to prove that treating hyperlipidemia has a positive influence on nitric oxide-mediated renal functions.
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PMID:Impact of nitric oxide on renal hemodynamics and glomerular function: modulation by atherogenic lipoproteins? 881 12

New evidence suggests an interaction between hyperlipidemia, activation of the renin-angiotensin system, and atherosclerotic disease. In patients with atherosclerosis and hyperlipidemia, coronary endothelial dysfunction is usually diffuse and affects vasomotor tone, platelet activity, thrombosis, fibrinolysis, and regulation of inflammatory cells. Angiotensin II, an important oxidant, alters the binding of low-density-lipoprotein (LDL) cholesterol to its receptors and increases endothelial uptake of LDL. Endothelial dysfunction is worsened by the suppression of nitric oxide production and/or release via angiotensin II-associated degradation of bradykinin and oxygen free radical production, resulting in inadequate vasorelaxation. Therapy with angiotensin-converting enzyme (ACE) inhibitors appears to eliminate these untoward effects and may ameliorate the tendency for myocardial infarction associated with elevated plasma levels of angiotensin II. Although the role of ACE inhibitors in the prevention and/or treatment of coronary artery disease in patients without left ventricular dysfunction remains to be established, the capacity of ACE inhibition to correct endothelial dysfunction offers promise. The ability of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors to improve endothelial function, prevent the progression of coronary atherosclerosis, reduce the incidence of ischemic events, and improve survival is well known. Potentially, ACE inhibitors may have an additive or synergistic effect on the development of atherosclerosis and the clinical consequences of this disease when used in combination therapy with lipid-lowering strategies.
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PMID:The potential use of angiotensin-converting enzyme inhibitors in patients with hyperlipidemia. 912 18

The renin-angiotensin system is an important modulator of arterial blood pressure and inhibitors of the angiotensin-converting enzyme (ACE-Is) and are currently used in the treatment of hypertension. The pleiotropic actions exerted by angiotensin II (AngII) on the functionality of the vessel wall may have pro-atherosclerotic outcomes; evidence for an anti-atherosclerotic effect of ACE-Is has been presented and an antioxidant effect has been attributed to thiol-containing ACE-Is, like Captopril. The present study has been undertaken to investigate the effect of Delapril, a lipophilic ACE-I, on the development of atherosclerosis in cholesterol-fed rabbits. While it did not correct hyperlipidemia, Delapril dose dependently inhibited the development of atherosclerosis, expressed as aortic area covered by lesions (23.3+/-4.1, 21.3+/-2.4 and 18.5+/-3.3% with Delapril at the daily dose of 5, 10 and 20 mg/kg, respectively, versus 38.2%+/-6.4 for control animals) and its effect was similar to that of Captopril (14.5+/-5.1% at the daily dose of 25 mg/kg). Furthermore, Delapril partially and dose dependently restored endothelium-dependent relaxation, which is impaired in vessels from hypercholesterolemic animals (51.80+/-12.18, 59.74+/-5.16, 69.13+/-8.70 maximal percent relaxation versus 48.26+/-3.05% for the untreated control and 67.67+/-6.72% for Captopril-treated animals). An antioxidant mechanism is unlikely to explain this data, since Delapril does not contain thiol groups. These observations suggest that Delapril may represent an effective pharmacological approach for the treatment of atherosclerosis during its early phases.
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PMID:Delapril slows the progression of atherosclerosis and maintains endothelial function in cholesterol-fed rabbits. 956 38

The spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat is a genetic model that exhibits both non-insulin-dependent diabetes mellitus (NIDDM) and hypertension. To determine the impact of long-term treatment with the long-acting angiotensin-converting enzyme (ACE) inhibitor perindopril (PE) on the glucose metabolism, lipid levels, and heart in this model, studies were performed in three groups of SHR/N-cp rats maintained on a diet containing 54% carbohydrate with 18% sucrose and 36% starch. One group of obese rats received PE (0.5 to 1.0 mg/kg body weight/d) for 3 to 4 months, a second group of obese rats received no treatment, and a third group of lean rats were used as controls. The mean systolic blood pressure (SBP) increased gradually in both untreated obese and lean rats, with lean animals showing slightly higher levels compared with untreated obese rats. By contrast, SBP was reduced to normal levels in PE-treated obese rats throughout the treatment period. Compared with lean rats, obese rats showed significantly higher body weight and fasting serum levels of glucose, insulin, total cholesterol (TC), and triglyceride (TG). However, no significant differences were observed in these metabolic parameters between PE-treated and untreated obese rats. Plasma renin activity measured at the end of the treatment period was significantly higher in PE-treated rats compared with untreated obese and untreated lean rats. The mean heart weight and left ventricular weight, expressed in absolute terms or indexed to body weight, were significantly lower in PE-treated versus untreated obese and untreated lean rats. To further determine whether glucose metabolism is directly affected by PE treatment, in vitro glycogen synthesis was evaluated in isolated soleus muscles obtained from three additional groups of animals. The basal rate of muscle glycogen synthesis was significantly lower in obese compared with lean rats (P < .05), but did not differ between PE-treated and untreated obese rats. Maximal insulin-stimulated glycogen synthesis increased threefold in PE-treated obese rats, but this increase did not differ from the increases observed in untreated obese and lean rats. In conclusion, the present study shows that long-term PE treatment in obese SHR/N-cp rats with NIDDM and hypertension effectively controlled systemic arterial pressure and resulted in a significant reduction in left ventricular weight. However, these favorable effects of PE were not associated with significant improvement in glucose tolerance, hyperinsulinemia, and hyperlipidemia in this model. PE also had no direct stimulatory effects on either basal or insulin-mediated glycogen synthesis in the isolated soleus muscle of obese rats, perhaps because of the severe insulin-resistant state of the animals. Our results support the clinical observations that antihypertensive therapy with ACE inhibitors has neutral effects on glucose metabolism and insulin sensitivity in patients with combined hypertension and NIDDM.
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PMID:Long-term effects of perindopril on metabolic parameters and the heart in the spontaneously hypertensive/NIH-corpulent rat with non-insulin-dependent diabetes mellitus and hypertension. 978 21


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