Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is well known that changes in serum potassium cause ventricular arrhythmias as a result of clearly documented changes in the electrophysiological characteristics of single fibers. Hypopotassemia induced by thiazide and loop diuretics may contribute to the incidence of sudden cardiac death in patients with hypertension and those with congestive heart failure. In addition, hypopotassemia appears to be an independent risk factor for lethal ventricular arrhythmias occurring in the setting of acute myocardial infarction and contributes significantly to arrhythmias associated with starvation and alcoholism. The increase in myocardial extracellular potassium that occurs in the ischemic zone after coronary occlusion is clearly a major factor in the genesis of lethal ventricular arrhythmias that occur in this setting. A decrease in serum magnesium is also believed to be arrhythmogenic, and magnesium depletion is thought to play a role in many of the arrhythmias associated with hypopotassemia. Moreover, the administration of magnesium salts may be effective in the management of life-threatening ventricular arrhythmias. However, definite evidence establishing a causal relation between ventricular arrhythmias and hypomagnesemia or intracellular magnesium depletion is lacking. Changes in intracellular calcium contribute to the arrhythmias associated with acute ischemia and with reperfusion and may be important in the genesis of ventricular tachycardia induced by exercise and by digitalis. Thus, electrolyte and metabolic abnormalities clearly underlie lethal ventricular arrhythmias in a wide variety of clinical situations and should be routinely considered as potential etiologic factors in patients with life-threatening ventricular arrhythmias, particularly those with hypertension and congestive heart failure who are receiving thiazide and loop diuretics.
 ...
PMID:Electrolyte abnormalities underlying lethal and ventricular arrhythmias. 172 8

Diet clearly influences neurotransmission. This can be important in grossly undernourished children. It can also be important in children in whom normal homeostatic mechanisms governing food intake are bypassed. Subtle differences in behavior can occur with physiologic variation in food intake. Components of foods can also be used as drugs. Starvation can impair neuronal maturation and can have lasting effects upon behavior and intellectual performance. The extent of starvation's impact upon the brain depends upon whether undernutrition occurred during a critical phase in brain development. Short-term fasting has small, but significant, effects upon intellectual performance. Even when gross malnutrition is not present, subtle changes in diet may modulate brain function. Tryptophan, tyrosine, and choline in the diet are used as precursors for neuronal synthesis of serotonin, dopamine and norepinephrine, and acetylcholine, respectively. It is likely that the brain's sensitivity to certain components of the diet exists to permit monitoring of food intake by the central nervous system. Tryptophan, tyrosine, and choline may be useful in treatment of humans with sleep disorders, pain depression, mania, hypertension, shock, or dyskinesias. Other components of the diet that may affect behavior include food additives, sugar, and caffeine. Food additives may exacerbate hyperactive symptoms in a small proportion of children with attention deficit disorder. Given that there is little potential for harm and that there is a subpopulation that may respond, a trial of a diet that contains no food additives may be a valid diagnostic approach for children with attention deficit disorder who do not respond to stimulant therapy or for children for whom stimulant therapy is not desired. Refined sugar has been blamed for many behavioral abnormalities. Subtle effects of carbohydrate upon behavior have been reported, but the existing data do not support the hypothesis that sucrose or fructose exert special effects upon neurotransmission. Caffeine is easily detected as a stimulant by humans, but it has little effect upon cognitive function. Administration of large doses of vitamins has no beneficial effect in most humans with schizophrenia, attention deficit disorder, autism, Down's syndrome, or drug addiction. Large doses of niacinamide may even be harmful, as they may cause hepatic damage.
 ...
PMID:Dietary influences on neurotransmission. 302 51

A novel model of nutritionally induced hypertension in the rat is described. Dietary obesity was produced by providing sweet milk in addition to regular chow, which elicited a 52% increase in caloric intake. Despite 54% greater body weight gain and 139% heavier retroperitoneal fat pads, 120 days of overfeeding failed to increase systolic pressure in the conscious state (125 +/- 8 vs. 121 +/- 4 mmHg in chow-fed controls) or mean arterial pressure under urethan anesthesia (71 +/- 4 vs. 63 +/- 3 mmHg). In contrast, mild hypertension developed in intermittantly fasted obese animals (a 21-mmHg increase in systolic blood pressure measured in the conscious state and a 16-mmHg increase in mean arterial pressure under anesthesia relative to chow-fed controls). The first 4-day supplemented fast was initiated 4 wk after the introduction of sweet milk, when the animals were 47 g overweight relative to chow-fed controls. Thereafter, 4 days of starvation were alternated with 2 wk of refeeding for a total of 4 cycles. A rapid fall in systolic blood pressure (12 +/- 2 mmHg at 2 days) accompanied the onset of supplemented fasting and was maintained thereafter (2.7 +/- 2.6 mmHg further decrease during the latter half of the fast). With refeeding, blood pressure rose precipitously (13 +/- 3 mmHg in the 1st 2 days), despite poststarvation anorexia. Blood pressure tended to rise slightly over the remainder of the realimentation period (5.2 +/- 2.8 mmHg). After the 4th supplemented fast, hypertension was sustained during 30 days of refeeding. Cumulative caloric intake in starved-refed rats fell within 2% of that in chow-fed controls.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Refeeding hypertension in dietary obesity. 333 69

To delineate the hormonal mechanism of dietary-induced changes in sodium balance, the role of insulin and glucagon in natriuresis of fast was evaluated in obese subjects submitted to a total starvation and given either glucagon or somatostatin infusion on day 4 of fast. While large amounts of glucagon (1 mg over 6 h) stimulated concomitantly ketonaemia, ketonuria and renal sodium losses, the ten-times lower amounts of glucagon induced an increase in renal ketone body and sodium excretion without any significant change in ketonaemia. It was concluded, therefore, that elevated plasma glucagon level may enhance renal sodium loss in ketotic states, through a direct renal effect reducing tubular ketone body reabsorption, hence increased ketonuria and natriuresis. It appears nevertheless that decreased insulin secretion, rather than an increase in plasma glucagon level must be considered as a key hormonal factor responsible for natriuresis attending starvation. Indeed, the concomitant reduction in plasma glucagon and insulin levels, resulting from somatostatin infusion on day 4 of fast, was followed by significant increase in natriuresis. The latter observation supports several previous studies indicating that insulin stimulates sodium reabsorption by the kidney and that the reduction in insulin secretion may induce an increase in renal sodium excretion. It was concluded, therefore, that not only sodium intake but also the carbohydrate content of the diet should be reduced in an attempt to induce a negative sodium balance and to correct hypertension in obese subjects.
 ...
PMID:Influence of insulin and glucagon on sodium balance in obese subjects during fasting and refeeding. 611 18

Over the last ten years a large body of information has accumulated which indicates that physiologic changes in the plasma insulin concentration are capable of affecting electrolyte transport by the kidney as well as by variety of other tissues. In the present discussion the effect of insulin on the renal handling of sodium, potassium, phosphate, and calcium is reviewed, with an emphasis on sodium transport (Table 1). An attempt is made to relate the effects of insulin on sodium metabolism to four common clinical situations: (a) hypertension and obesity, (b) sodium wasting in diabetes mellitus, (c) natriuresis of starvation, and (d) sodium retention and edema following refeeding.
 ...
PMID:Insulin and renal sodium handling: clinical implications. 701 90

Data are discussed which demonstrate that insulin plays an important role in sodium metabolism. The primary action of insulin on sodium balance is exerted on the kidney. Increases in plasma insulin concentration within the physiological range stimulate sodium reabsorption by the distal nephron segments and this effect is independent of changes in circulating metabolites or other hormones. Several clinical situations are reviewed: sodium wasting in poorly controlled diabetics, natriuresis of starvation, anti-natriuresis of refeeding and hypertension of obesity, in which insulin-mediated changes in sodium balance have been shown to play an important pathophysiological role.
 ...
PMID:The effect of insulin on renal sodium metabolism. A review with clinical implications. 702 50

Changes in cardiac protein composition occur in a variety of patho-physiological situations and are usually accompanied by modifications in protein synthesis. Although adjustments in protein synthesis during starvation may be adaptive, the alterations in protein synthesis seen in response to ethanol ingestion may be pathological and an important step in the genesis of alcoholic heart muscle disease. The alterations in heart muscle in hypertension are initially adaptive but in the long term they are deleterious, and involve both transcription and translation. While adequate methods exist for quantifying the amount of mRNA for contractile and non-contractile proteins, such studies of gene-expression provide no dynamic information on the rate at which tissue proteins are lost or accrued. This can only be determined by measuring the rate of protein turnover, i.e. either protein synthesis or protein breakdown. Techniques for directly determining the rates of protein breakdown are limited or involve surgical procedures. Methods for measuring the rate of protein synthesis are described, and are illustrated by their application to the investigation of starvation and ethanol toxicity. In particular, attention is focused on the fact that reliable rates of protein synthesis are obtained only if the specific radioactivity of the precursor at the site of protein synthesis (aminoacyl-tRNA) is assessed.
 ...
PMID:Protein synthesis in the heart in vivo, its measurement and patho-physiological alterations. 759 36

In previous studies, we related increased elastolytic activity in pulmonary arteries (PA) with endothelial injury to the later development of PA hypertension in rats. As the mechanism causing the increased PA elastase was unknown, we hypothesized that serum factors which are accessible to vascular smooth muscle cells (SMC) following endothelial injury stimulate their elastolytic activity. To test this, we developed an in vitro assay in which we added [3H]-elastin to cultured vascular SMC after 24 h serum starvation and monitored elastolysis following a further 24 h incubation with fetal bovine serum (FBS). We observed that serum induced increased elastolytic activity in both PA and aorta-derived SMC but not in endothelial cells or SMC with low basal levels of elastolytic activity. Maximum stimulation of SMC elastolytic activity occurred with a concentration as low as 1% FBS and despite elastase inhibitors in serum, suggesting that the activity is confined to the immediate pericellular region where enzyme concentration is high. Serum-stimulated elastolytic activity was not reproduced by growth factors or cytokines known to be associated with vascular disease or to induce release of elastases in other cells. The serum inducing elastolytic activity was heat and acid labile. It was associated with increased elastin adhesion to the 67 kD elastin binding protein on SMC surfaces and was prevented by tyrosine kinase inhibitors but not protein kinase C or A inhibitors. Our studies therefore suggest a mechanism whereby serum induction of SMC elastase requires signalling through the elastin binding protein and activation of tyrosine kinase.
 ...
PMID:Serum-induced vascular smooth muscle cell elastolytic activity through tyrosine kinase intracellular signalling. 802 Dec 92

Type 2 diabetes is likely to be a polygenic disease, with a combination of major and minor genes affecting obesity, insulin secretion, and insulin action. Amongst these inputs, the 'thrifty genotype' hypothesis is most likely to apply to the predisposition to develop obesity, since the ability to store scarce fuels in periods of starvation could lead to obesity given a western lifestyle. Other genetic variations that were neutral with respect to food deprivation could be harmful with food excess. These could include 'defects' in islet cell function: examples could be mutations in the glucokinase gene and the genetic factors leading to amyloid deposition. The occurrence of associated lipid abnormalities or hypertension is probably due to additional specific genetic determinants that also become exaggerated by a modern lifestyle. The interactions between different genetic and environmental inputs are complex, and will probably be elucidated piecemeal as different genetic determinants are identified.
 ...
PMID:Complex genetics of type 2 diabetes: thrifty genes and previously neutral polymorphisms. 821 Feb 95

The availability of food and the nutritional status of western Europeans have never been so good as in recent decades. However, we have not to go back too long to see that severe malnutrition also occurred in parts of western Europe. An example was the malnutrition and starvation causing high death rates in the western Netherlands in the early months of 1945, just before the end of the Second World War. Today there is an abundance of food in western Europe. Nevertheless we do warn people that the food, nutritious and delicious as it is, may be hazardous to health. Degenerative diseases like cardiovascular diseases, cancer, diabetes, obesity, osteoporosis and hypertension are very prevalent in our society. It is very likely that certain nutrients in foods do contribute both to the causes and prevention of these diseases. In this paper some new findings of the role of diet in health will be reviewed. This will be followed by a brief discussion on the status of nutrition research and training in Europe. Finally attention is asked for the need to start building-up a programme for nutritional leadership in Europe.
 ...
PMID:The future of nutrition in Europe. 826 9


1 2 3 4 5 Next >>