UMLS:C0023890 - FACTA Search

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Query: UMLS:C0023890 (cirrhosis)
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Alpha-human atrial natriuretic polypeptide (alpha-hANP) was applied to 16 clinical patients, 6 patients with essential hypertension, 7 patients with congestive heart failure and 3 patients with cirrhosis. Following intravenous bolus injection of 400 micrograms of synthetic alpha-hANP, a hypotensive effect of very rapid onset was found, which was more potent in the hypertensive patients than in the normotensive cases. Cardiac functions were improved significantly with a similar time course as the depressor response in the cases of heart failure or hypertension. Hemodynamic observations showed a marked increase in cardiac output, cardiac index, stroke volume, ejection fraction and ejection rate, and a concomitant decrease of the pressure in the right side of the heart and pulmonary circulation in these subjects. In addition, the renal response to alpha-hANP induced obvious increases in urine volume, electrolytes and creatinine excretions in all the subjects. Finally, plasma levels of aldosterone, Arg-vasopressin and noradrenaline were also altered by alpha-hANP. No significant side effects were registered. The above result confirms the therapeutic actions of alpha-hANP in human subjects and opens the possibility to research alpha-hANP as a powerful pharmacological tool as well as potential new medicine for human disorders.
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PMID:Therapeutic actions of alpha-human atrial natriuretic polypeptide in 16 clinical cases. 295 43

An explosion of research over the last seven years has led to the discovery and characterization of a peptide, originating in the heart's atria, that possesses impressive vasorelaxant and natriuretic properties. Although the several atrial peptides that have been isolated by researchers working in different laboratories vary in length, all contain the same core sequence. Cardionatrin I, a 28-amino acid peptide, is the likely active circulating hormone. In the atrial peptide's action on vascular smooth muscle, it appears especially to counter the effects of angiotensin II. The peptide's effects on renal hemodynamics and sodium excretion include a marked increase in glomerular filtration rate. Atrial hormone also induces impressive natriuresis in experimental animals, for which an increase in glomerular filtration rate may be a necessary component. Atrial hormone has been found to reduce arterial blood pressure in both animals and humans. In experimental animals, the peptide appears to lower blood pressure by different mechanisms in high- and low-renin forms of hypertension, and to lower pressure to a greater degree and with lower doses in the former as compared with the latter. In patients with essential hypertension, primary aldosteronism, congestive heart failure, renal failure, and perhaps ascitic cirrhosis, plasma ANH levels tend to be higher than they are in normotensive individuals. Atrial hormone causes marked and sustained suppression of renal renin secretion and, thus, of plasma renin levels. In addition, atrial hormone blocks aldosterone secretion and opposes the vasoconstrictive effects of angiotensin II and the sodium-retaining action of aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atrial natriuretic hormone: a regulator of blood pressure and volume homeostasis. 297 65

The renin-angiotensin-aldosterone system plays an important role in the development and maintenance of high blood pressure in several forms of hypertension. In hypertensive patients with primary aldosteronism, antimineralocorticoids are, as expected, very effective in reducing blood pressure and correcting metabolic disturbances. In patients with essential hypertension, an abnormal relationship between angiotensin II and aldosterone can occur. Aldosterone secretion in these patients is often too high relative to circulating levels of angiotensin II. Antimineralocorticoids effectively lower blood pressure in a large number of these patients. The reactive hyperreninemia caused by salt depletion is a factor limiting the antihypertensive effect of natriuretic agents including that of antimineralocorticoids. The enhanced aldosterone secretion resulting from treatment with a diuretic other than an antimineralocorticoid may diminish the natriuretic action of that diuretic. Therefore, antimineralocorticoids given in addition to a diuretic enhance natriuresis. The renin-angiotensin-aldosterone system is also involved as a compensatory mechanism in cardiovascular and body fluid homeostasis of patients with severe congestive heart failure or liver cirrhosis with ascites. Antimineralocorticoids are very effective in such conditions. In patients with congestive heart failure treated with digitalis, these natriuretic agents are particularly useful because of their potassium-sparing properties. The risk of developing hyperkalemia during antimineralocorticoid administration is negligible unless renal function is impaired. Antimineralocorticoids have the advantage of exerting no deleterious effect on carbohydrate and lipid metabolism. The use of these agents seems therefore rational in a variety of diseases concerned with blood pressure and body fluid volume regulation.
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PMID:Clinical applications of antimineralocorticoids. 305 64

Measurements of total body potassium (T.B.K.) were made by whole-body counting in four groups of patients receiving oral frusemide for one year. Patients in group 1 had essential hypertension and normal renal function and received 40 mg frusemide daily without potassium supplements. Patients in group 2 were similar but received oral potassium supplements for the first four months of treatment. Patients in group 3 had hypertension associated with renal disease and received 120 mg frusemide daily without potassium supplements. Patients in group 4 also had hypertension and renal impairment and in addition to 120 mg frusemide daily they received oral potassium supplements for four months. No evidence of depletion of T.B.K. was found in any of the groups after continuous treatment with frusemide for one year. It is questioned whether potassium supplementation in long term diuretic therapy with frusemide is necessary unless there is evidence of pre-existing potassium depletion or of some other factor such as cardiac failure, cirrhosis of the liver, or the nephrotic syndrome.
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PMID:Total body potassium in long-term frusemide therapy: is potassium supplementation necessary? 421 34

Out of all until now discovered natriuretic factors it is still the atrial natriuretic factor (ANF) which is the most significant with its diuretic, natriuretic and vasodilatory effects. Its effect is antagonistic to sodium retention factors. The increase of its levels in arterial hypertension is more of secondary character, but according to some authors the functional deficit of ANF secretion can be applied also primarily in the development and maintenance of high blood pressure. ANF levels represent a good marker of the clinical severeness and are of prognostic value. Increased levels were detected also in cases of renal failure and partially in hepatic cirrhosis. Natriuretic hormone, in comparison to ANF, is a natriuretic and vasoconstrictive substance, the effect of which is based on the mechanism of sodium pump inhibition. Chemically the main candidate is represented by endogenous ouabain, or a digitalis-like activity. It increases physiologically due to the expansion of extracellular fluid during gravidity and in newborn. Its pathological increase is brought about by some forms of essential hypertension and in the diseases associated with fluid retention and edema development. Cirrhosis of the liver can reflect both the degree of sodium retention and haemodilution, as well as the severeness of hepatic lesion. (Tab. 2, Ref. 30.).
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PMID:[The clinical significance of natriuretic hormones]. 862 37

Sympathetic nervous system activation has been documented in several cardiovascular disorders. In some, characterized by cardiac failure and portal hypertension accompanying hepatic cirrhosis, the sympathetic nervous stimulation is reflex and, to some extent, compensatory but has adverse consequences. For example, in cardiac failure, the sympathetic nerves of the heart are preferentially stimulated, providing adrenergic support to the failing myocardium but at the probable cost of arrhythmogenesis and progressive myocardial deterioration. The sympathetic activation present in patients with essential hypertension, which involves the sympathetic outflows to skeletal muscle, heart, and kidneys and is seen particularly in younger patients, differs from these examples in that the sympathetic nervous stimulation is apparently not reflex and the primary cause is unknown. There is, however, evidence that activation of forebrain pressor noradrenergic nuclei may be of importance as an underlying central nervous system mechanism. This sympathetic nervous stimulation in patients with essential hypertension, in addition to initiating the blood pressure elevation, may also contribute to the commonly associated metabolic abnormalities of insulin resistance and hyperlipidemia, with neural vasoconstriction having metabolic consequences, impairing glucose delivery and causing insulin resistance in muscle, and retarding postprandial clearing of lipids in liver. Trophic effects of sympathetic activation on cardiovascular growth are claimed but have yet to be demonstrated conclusively in humans.
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PMID:Sympathetic nervous system: contribution to human hypertension and related cardiovascular diseases. 864 1

1. Adrenomedullin is a potent vasodilating peptide first isolated from phaeochromocytoma and adrenal medulla but also found in the heart, lungs and kidneys. It may also be a paracrine factor because endothelial and smooth muscle cells synthesize adrenomedullin as well as express the receptors. Adrenomedullin induces vasorelaxation by activating adenylate cyclase and also by stimulating the release of nitric oxide. 2. We have developed a specific radioimmunoassay and measured the immunoreactivity of human adrenomedullin in the plasma of 58 male subjects: eight with essential hypertension, 12 with heart failure, 10 with ascites due to cirrhosis, 12 with chronic renal failure, four with hypoxia due to chronic obstructive pulmonary disease and 12 control subjects. 3. Plasma levels (mean +/- SEM) in patients with essential hypertension (16.3 +/- 1.9 pmol/l), congestive heart failure (17.5 +/- 2.8 pmol/l) and renal failure (17.7 +/- 2.5 pmol/l) were raised compared with control subjects (7.8 +/- 1.4 pmol/l, P < 0.05), confirming previous reports. 4. In addition, we observed that plasma levels of adrenomedullin were significantly raised in patients with ascites due to liver cirrhosis (15.5 +/- 1.9 pmol/l) and chronic obstructive pulmonary disease with hypoxia (20.0 +/- 1.5 pmol/l). 5. We concluded that the plasma level of adrenomedullin is raised in a variety of diseases.
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PMID:Elevated plasma levels of human adrenomedullin in cardiovascular, respiratory, hepatic and renal disorders. 903 92

A new, fast and reliable radioimmunoassay for measurement of brain natriuretic peptide (BNP) in human plasma has been developed and its application is reported in healthy subjects and in patients with congestive heart failure, chronic renal failure, liver cirrhosis and essential hypertension. The antibody was raised in rabbits, the tracer was made by the iodogen method and polyethylene glycol was used for separation of free and bound tracer. BNP was extracted from plasma using Sep-Pak C18 cartridges. The recovery of unlabelled BNP added to plasma was 77.5 +/- 6.2% (mean +/- SD). The detection limit in plasma was 0.55 pmol l-1. No cross-reactivity existed with the natriuretic peptides ANP, CNP or urodilatin. In 124 healthy subjects the mean BNP was 1.8 +/- 1.0 pmol l-1 (SD), range 0.6-5.5. BNP increased slightly with age, was higher in women than men and had no circadian rhythm. In eight patients with congestive heart failure the median BNP level was 30.5 pmol l-1, range 3.9-65.3. In 14 patients with chronic renal failure the median BNP level was 50.5 pmol l-1, range 10.9-219.8 before dialysis, and 38.0 pmol l-1, range 9.4-180.0 immediately following dialysis. In 25 patients with liver cirrhosis the median BNP value was 7.8 pmol l-1, range 1.2-43.1. There was no difference between patients with or without ascites. In 18 medically treated patients with essential hypertension the median BNP level was 5.0 pmol l-1, range 1.2-45.5 pmol l-1.
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PMID:A new, fast and reliable radioimmunoassay of brain natriuretic peptide in human plasma. Reference values in healthy subjects and in patients with different diseases. 935 73

Although the underlying mechanisms no doubt differ, activation of the sympathetic nervous system is an important pathophysiological feature in primary arterial hypertension, in portal hypertension accompanying hepatic cirrhosis, and in heart failure, and is a logical therapeutic target for centrally acting sympathetic nervous system suppressant drugs. Portal hypertension: The sympathetic outflows to skeletal muscle vasculature, the heart, the kidneys and to the hepatomesenteric circulation are stimulated in patients with alcoholic cirrhosis of the liver, perhaps as a reflex response to the vasodilatation and vascular shunting present. Acute dosing with clonidine produces dose dependent reduction in noradrenaline spillover from visceral organs and reduction in hepatic vein wedge pressure, with preservation of hepatic blood flow and negligible fall in arterial pressure. These findings indicate the clinical potential of drugs such as clonidine, moxonidine and rilmenidine for chronically lowering portal venous pressure in cirrhosis. Arterial hypertension: Activation of the sympathetic outflow to the heart, kidneys and skeletal muscle vasculature is commonly present in younger (< 45 years) patients with essential hypertension. The sympathetic stimulation appears to have adverse consequences in hypertensive patients beyond blood pressure elevation. Neural vasoconstriction in skeletal muscle has metabolic effects by impairing glucose delivery, which is a basis for insulin resistance and hyperinsulinemia. Within the heart a trophic effect of sympathetic activation on cardiac growth, contributing to the development of left ventricular hypertrophy, and an arrhythmogenic effect are also likely. Cardiac failure: The cardiac sympathetic nerves are preferentially stimulated in severe heart failure, with norepinephrine release from the failing heart at rest being increased as much as 50-fold, similar to the level seen in healthy people during near maximum exercise. This preferential activation of the cardiac sympathetic outflow contributes to arrhythmogenesis and possibly to progression of the heart failure, and has been directly linked to mortality; a high rate of spillover of noradrenaline from the heart is a strong, independent predictor of poor prognosis in severe cardiac failure. The mechanisms underlying sympathetic nervous stimulation are not entirely clear. Increased intracardiac diastolic pressure seems to be one peripheral signal, and increased forebrain norepinephrine turnover an important central mechanism. Following the demonstration of the beneficial effect of the beta-adrenergic blocker, carvedilol, and with second generation centrally acting sympathetic suppressants now under clinical investigation, elucidation of the abnormalities in central nervous control of sympathetic outflow in heart failure has become clinically relevant.
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PMID:Increased sympathetic nervous system activity and its therapeutic reduction in arterial hypertension, portal hypertension and heart failure. 985 71

Spironolactone, a competitive aldosterone receptor antagonist (ARA), has traditionally been the treatment of first choice in idiopathic hyperaldosteronism (IHA) and for preoperative management of aldosterone producing adenoma (APA). Spironolactone is partially absorbed, is extensively metabolized mainly by the liver and its therapeutic properties are attributable to active metabolite canrenone. At therapeutic doses of 25 to 400 mg per day, spironolactone effectively controls blood pressure and hypokalemia in the majority of cases. Endocrine side effect are often associated and mainly consist of gynecomastia, decreased libido and impotence in man and menstrual irregularities in women. Canrenone and the K+ salt of canrenoate are also in clinical use: they avoid the formation of intermediate products with anti-androgenic and progestational actions, resulting in a decreased incidence of side effects. Furthermore, a relatively new selective ARA compound (eplerenone) with reduced affinity for androgen and progesterone receptors, is currently undergoing clinical trials. In essential hypertension aldosterone can contribute to hypertension and increases the incidence of myocardial hypertrophy and cardiovascular events. On the other hand, inhibition of Renin-Angiotensin-Aldosterone System (RAAS) is associated with a decrease in blood pressure, with a regression of left ventricular hypertrophy and a reduction of target organ damage. Thus, ARA have been proposed as complementary treatment associated to ACE inhibitors and angiotensin receptor antagonists. Aldosterone is also known to play an important role in pathophysiolgy of congestive heart failure (CHF). In vitro and in vivo evidences suggest that aldosterone promotes myocardial fibrosis. This effect reflects direct, extra-epithelial actions of aldosterone via cardiac MR which are counteracted by ARAs in animal models. The RAAS is chronically activated in CHF. Non potassium-sparing diuretics further stimulate the RAAS and cause hypokalemia. Thus, use of ARAs in CHF was first proposed to correct potassium and magnesium depletion. At present ARAs are indicated in the management of primary hyperaldosteronism, in oedematous conditions in patients with CHF, in cirrhosis of the liver accompanied by oedema and ascites, in essential hypertension and in hypokalemic states. Its indication as adjunctive therapy of heart failure is currently under investigation. In fact, it is well known that even high doses of ACE inhibitors may not completely suppress the RAAS; aldosterone 'escape' may occur through non angiotensin II dependent mechanisms. Addition of spironolactone to an ACE inhibitor causes marked diuresis and symptomatic improvement. During the last few years, the RALES study (Randomized Aldactone Evaluation Study) was organized to explore the efficacy of combination therapy with spironolactone and ACE inhibitor in patients with CHF, class III or IV NYHA. The study was stopped 18 months early because the results were so statistically and clinically significant that it would be unethical to continue the trial. It is reported a 30 percent decrease in mortality and hospitalisation for cardiac causes in spironolactone-treated group vs placebo group.
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PMID:Aldosterone antagonists in hypertension and heart failure. 1079 May 93

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