Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In rats with unilateral renal artery stenosis, the malignant phase of hypertension is characterized by: systolic blood pressure above 180-190 mm Hg; sodium and water loss; polyuria and polydipsia; markedly activated renin-angiotensin-aldosterone system; impairment of renal function and malignant nephrosclerosis in the contralateral kidney; some rats exhibit signs of cerebral hemorrhage, heart failure, acute renal failure, and some rats die. After such a phase of malignant hypertension, a period of remission may occur, which is followed by another malignant phase, etc. When malignant hypertensive rats are offered, in addition to water, saline as drinking fluid, they compulsively drink the saline, BP falls transiently, and all signs of malignant hypertension nearly or completely disappear. These observations indicate that, at a critically high BP level, it is salt and water loss which, by activating the renin-angiotensin system, trigger the vicious circle of malignant renal hypertension in rats.
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PMID:Pathogenesis of malignant hypertension: experimental evidence from the renal hypertensive rat. 119 18

Renal hypertension can usually be recognized only by examining all the features of the hypertensive illness. On the other hand, the investigation of a case of hypertension whose genesis was previously unclear can lead to the diagnosis of a hitherto unrecognized renal disease. The blood pressure values found in patients with renal hypertension are of widely differing degrees of severity. Slight rises in blood pressure (e.g. 140/90 mm Hg), can be a sign of renal disease in adolescent patients. 10-15% of the cases of chronic renal hypertension develop into malignant hypertension. High diastolic values above 120 mm Hg without renal symptomatology and without reduced renal function speak against a primary renal cause of the rise in blood pressure. The finding of hypertension developing during the course of renal disease is, with respect to the hypertensive cardiovascular complications, just as important as in the case of essential hypertension. Complications which can occur during renal hypertension include cardiac insufficiency, hypertensive encephalopathy, retinopathy, hypertensive crises and acceleration of the renal disease.
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PMID:The clinical picture of renal hypertension. 119 21

Based on animal experiments in rats (spontaneous and renal hypertension, experimental aortic stenosis, thyroxine and training-induced hypertrophy, and aorto-caval fistula with and without additional unilateral renal artery coarctation) as well as clinical data and literature, the functional consequences of cardiac hypertrophy and structural ventricular dilatation are analyzed and discussed. A methodological approach, developed on the basis of Frank's diagram and model calculations, permits quantitatively estimating the significance of ventricular geometry (wall thickness and inner dimensions) compared to myocardial alterations (decrease in contractility and distensibility) and hemodynamic load (preload and systolic pressure). As a rule, hypertrophy causes an increase in ventricular working capacity, which allows the heart to cope with an increased hemodynamic load without a decrease in stroke volume and without enhanced systolic stress requirement. Adverse consequences mainly concern ventricular compliance, cardiac energetics, and electrophysiological parameters. Particularly from the example of the aorto-caval fistula, it can be seen that enhanced systolic wall stress does not necessarily lead to heart failure within a few months. However, the length of time for which the additional wall stress, with correspondingly increased energy demand, can be tolerated remains to be determined. In later stages, a multitude of alterations on the cellular, tissue, and organ level occurs, affecting myocardial and ventricular mechanics and energetics, depending on the type, velocity of development, and duration of overload. A distinction should be made between the adverse alterations, which can be related to myocardial growth, and those that are not necessarily related to a certain cell size (receptors, transformation of the contractile proteins) as well as those changes that do not primarily influence the myocardial cell (arteriosclerosis, microangiopathy). Structural dilatation alone could lead to insufficiency only in the case of substantial increase in inner ventricular radius. Reduced contractility, myocardial distensibility, and increased pressure load aggravate the negative effects of dilatation in a predictable manner, as demonstrated on the basis of a representative case of dilative cardiomyopathy. Using the example of spontaneously hypertensive rats, it is shown that ventricular mass and shape are differently influenced by various blood-pressure lowering agents, e.g., atenolol, nifedipine, and dietary interventions. It is concluded from the analysis of chronic cardiac reactions that adaptive processes are, in principle, ambiguous in character, revealing negative components even in the case of regular adaptation. However, it seems unjustified to aim at a regression of hypertrophy without reducing the underlying hemodynamic overload.
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PMID:Functional consequences of cardiac hypertrophy and dilatation. 182 78

To determine the adaptation of coronary vasculature and microvasculature to cardiac failure, renal hypertension was produced in rats, and the animals were killed 8 mo later when severe impairment in left ventricular function was present. By use of a new morphometric approach, it could be demonstrated that length densities of arteries from 6 to 20 microns in luminal diameter decreased by 23 and 26% in the midmyocardium and endomyocardium, respectively, whereas arteries ranging from 21 to 40 microns were reduced by 59, 55, and 46% in the outer, middle, and inner layers, respectively, of the left ventricular wall. In contrast, capillary density increased by 29 and 38% in the epimyocardium and endomyocardium, respectively. Capillary proliferation resulted in a 15% decrease in average diffusion distance for oxygen to the myocyte compartment of the tissue. Despite these opposite effects that may tend to compensate each other, the volume percent of collagen in the wall augmented by 106%. In conclusion, differences exist in the response of the coronary vascular tree to long-term renal hypertension that may impair coronary resistance and flow without affecting the capillary network and the oxygenation potential of muscle cells.
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PMID:Loss of intermediate-sized coronary arteries and capillary proliferation after left ventricular failure in rats. 203 75

A comparative study of the myocyte nucleolar organizer activity (NOA) was performed on silver-stained myocardium from 6 patients who had died from the hypertension disease and 7 others patients with secondary renal hypertension non-complicated by severe coronary atherosclerosis and heart failure. In the first group, positive correlations between NOA of cardiac cells and the level of maximal diastolic pressure (r = 0.8, p less than 0.028), wall thickness of the left ventricle (r = 0.8, p less than 0.028) as well as myocardial weight (r = 1.0, p less than 0.001) were found. In the second group, on the contrary, there was a pronounced negative correlation between NOA of the myocytes and myocardial weight (r = -0.86, p less than 0.005) which may be explained partially by a primary metabolic myocardial deficiency in such patients.
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PMID:[Activity of the nucleolar organizers in cardiomyocytes of patients with arterial hypertension of varying genesis]. 280 43

The sequence of atrial natriuretic factor (ANF) has been determined, as well as the complete structure of the rat and human complementary DNA and gene. ANF and ANF messenger RNA are present not only in atria but also in ventricles. The circulating form of ANF has been identified as the C-terminal of the molecule, ANF (Ser 99-Tyr 126). The isolated secretory granules of rat atrial cardiocytes contain only pro-ANF (Asn 1-Tyr 126). An enzyme (IRCM-SP1) has been isolated from heart atria and ventricles. This enzyme is highly specific in cleaving ANF (Asn 1-Tyr 126), to yield ANF (103-126), (102-126), and (99-126). In target cells, ANF produces a rise in cyclic guanosine 3',5'-monophosphate (cGMP) due to activation of particulate guanylate cyclase, and inhibition of adenylate cyclase leading in some cases to a decrease in cyclic adenosine 3',5'-monophosphate (cAMP). ANF produces relaxation of rabbit and rat aortic strips, inhibits steroidogenesis in both zona glomerulosa and zona fasciculata cells, and inhibits the release of arginine vasopressin from the isolated rat hypothalamohypophysial preparation in vitro but decreases AVP release in vivo only at pharmacological doses. In all forms of experimental hypertension, plasma levels of ANF are increased and, at some time periods, atrial levels are also decreased. The ventricular levels of immunoreactive ANF are also increased in renal hypertension. Infusion of ANF by minipumps decreases the blood pressure near control levels in several models of experimental hypertension. In cardiomyopathic hamsters with heart failure, the atrial levels of immunoreactive ANF are decreased while the plasma and ventricular levels are increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The heart as an endocrine gland. 282 60

During a 6 month observation period after operation, typical symptoms of congestive heart failure, such as cyanosis, systemic oedema, ascites and pleural effusion occur in the majority of rats which have a combined arteriovenous shunt (AV-shunt) and renal hypertension (Goldblatt II). In the present study, the left ventricle dilated to twice the size of that of age-matched Wistar controls. Developed wall stress increased significantly due to an augmented ratio of radius to wall thickness. Normalized stress-length (stress-midwall circumference) area and maximum rate of stress development (d sigma/dtmax) indicated decreased myocardial work and power capacity. Although the congestive symptoms can only partially be related to impaired cardiac function, this model may be useful for pathophysiological and pharmacological studies of chronic heart failure.
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PMID:Evaluation of left ventricular function in an experimental model of congestive heart failure due to combined pressure and volume overload. 337 42

Angiotensin converting enzyme inhibitors are effective therapy in hypertension. They are particularly useful in severe drug resistant or accelerated hypertension, in renal hypertension and in hypertensive heart failure. Although their exact mode of action has not been determined it is a consequence of the inhibition of angiotensin converting enzyme. They offer distinct advantages over conventional drugs in the treatment of high blood pressure particularly as they have no central or autonomic side effects and as a consequence the patients feel well. There is no postural effect on blood pressure and patients retain their normal cardiovascular reflex mechanisms and sexual function. They are particularly useful when combined with diuretics or salt restriction as not only do they have additive hypotensive effects but angiotensin converting enzyme inhibitors prevent the secondary hyperaldosteronism and hypokalemia associated with diuretic administration. Lastly, unlike many other forms of treatment for hypertension, renal blood flow and renal function tend to be maintained with converting enzyme inhibitors. Their overall role in the management of hypertension has yet to be determined, and the ultimate incidence of adverse effects after prolonged therapy is not yet known. They are however, an exciting new development in the treatment of hypertension.
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PMID:Treatment of hypertension with angiotensin converting enzyme inhibitors. 609 8

Both beta- and alpha-adrenergic mechanisms are important in the control of blood pressure; alpha-mediated vasoconstriction is responsible for the regulation of vascular tone, and beta-mediated responses stimulate the heart directly and indirectly by liberating renin and affecting vascular smooth muscle tone. beta-Adrenergic blocking drugs have long been established in the treatment of hypertension. The development of drugs which combine this action with an alpha-blocking effect represents an additional mode of action to lower the blood pressure. Numerous studies have demonstrated that labetalol intravenously or orally gives a rapid fall of blood pressure in essential and renal hypertension. It has also been used intravenously in phaeochromocytoma, tetanus, clonidine withdrawal, and as an adjunct to halothane to produce hypotensive anaesthesia. Intravenously, labetalol is probably best given as a graded infusion or as repeated small bolus injections to assure a smooth fall of blood pressure. Many long term studies have shown it to be effective orally in prolonged treatment of hypertension with studies of over 5 years, showing that tolerance does not develop. Labetalol can be used in combination with diuretics and other drugs when necessary. It can be employed to control the blood pressure in all grades of hypertension. A dosage of 100mg twice daily will often be adequate to control mild hypertension and the use of even lower doses has been reported. However, the dosage can be markedly increased in severe hypertension and while such doses are relatively exceptional, several trials have employed over 2 g per day for the more resistant cases. Studies have demonstrated that blood pressure control with labetalol is equivalent to that with beta-adrenoceptor blocking drugs plus vasodilators, or methyldopa. Labetalol has been used in patients with severe renal impairment and a number of studies suggest that it may now be the drug of choice in raised blood pressure of pregnancy. Side effects can be divided into those related to beta-blockade, those related to alpha-blockade and those not clearly related to either effect. It has been suggested that the side effects attributable to the beta-blocking component are less obtrusive than those seen with pure beta-blocking drugs without alpha-activity because the alpha-blockade modifies the consequences of beta-blockade. Heart failure has been reported, but for haemodynamic reasons would be expected to be less common; careful patient selection should avoid any risk. Similarly labetalol may worsen asthma even if the risks are probably less than with non-selective beta-blockade alone.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Combined alpha- and beta-receptor inhibition in the treatment of hypertension. 615 91

Labetalol is a combined alpha- and beta-adrenoceptor blocking agent for oral and intravenous use in the treatment of hypertension. It is a nonselective antagonist at beta-adrenoceptors and a competitive antagonist of postsynaptic alpha 1-adrenoceptors. Labetalol is more potent at beta that at alpha 1 adrenoceptors in man; the ratio of beta-alpha antagonism is 3:1 after oral and 6.9:1 after intravenous administration. Labetalol is readily absorbed in man after oral administration, but the drug, which is lipid soluble, undergoes considerable hepatic first-pass metabolism and has an absolute bioavailability of approximately 25%. There are no active metabolites, and the elimination half-life of the drug is approximately 6 hours. Unlike conventional beta-adrenoceptor blocking drugs without intrinsic sympathomimetic activity, labetalol, when given acutely, produces a decrease in peripheral vascular resistance and blood pressure with little alteration in heart rate or cardiac output. However, like conventional beta-blockers, labetalol may influence the renin-angiotensin-aldosterone system and respiratory function. Clinical studies have shown that the antihypertensive efficacy of labetalol is superior to placebo and to diuretic therapy and is at least comparable to that of conventional beta-blockers, methyldopa, clonidine and various adrenergic neuronal blockers. Labetalol administered alone or with a diuretic is often effective when other antihypertensive regimens have failed. Studies have shown that labetalol is effective in the treatment of essential hypertension, renal hypertension, pheochromocytoma, pregnancy hypertension and hypertensive emergencies. In addition, preliminary studies indicate that labetalol may be of value in the management of ischemic heart disease. The most troublesome side effect of labetalol therapy is posture-related dizziness. Other reported side effects of the drug include gastrointestinal disturbances, tiredness, headache, scalp tingling, skin rashes, urinary retention and impotence. Side effects related to the beta-adrenoceptor blocking effect of labetalol, including asthma, heart failure and Raynaud's phenomenon, have been reported in rare instances.
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PMID:Labetalol: a review of its pharmacology, pharmacokinetics, clinical uses and adverse effects. 631 May 29


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