UMLS:C0023890 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0023890 (cirrhosis)
42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II blockade with saralasin in human cirrhosis with ascites is associated with a significant reduction in arterial pressure, indicating that endogenous angiotensin II plays an important role in the maintenance of systemic hemodynamics in this condition. The aim of the current study was to investigate whether vasopressin also contributes to the maintenance of arterial pressure in cirrhosis with ascites. The study was performed using three groups of cirrhotic rats with ascites and three groups of control animals. The administration of d(CH2)5Tyr(Me)AVP, a selective antagonist of the vascular effect of vasopressin, to 10 cirrhotic rats induced a significant reduction in mean arterial pressure (from 94 +/- 4 to 85 +/- 4 mm Hg; P less than 0.001) and a significant increase in plasma renin activity (from 24.3 +/- 4.9 to 34.3 +/- 5.9 ng/mL.h; P less than 0.02) and plasma norepinephrine concentration (from 1474 +/- 133 to 2433 +/- 253 pg/mL; P less than 0.01). Similar results were observed following saralasin administration in a second group of 5 cirrhotic rats [mean arterial pressure decreased from 97 +/- 4 to 85 +/- 5 mm Hg (P less than 0.0001); and plasma renin activity and norepinephrine concentration increased from 18.4 +/- 5.8 to 40.3 +/- 5.7 ng/mL.h (P less than 0.02) and from 1383 +/- 70 to 2312 +/- 334 pg/mL (P less than 0.05), respectively]. The simultaneous blockade of angiotensin II and vasopressin in a third group of cirrhotic rats resulted in a significantly greater reduction of mean arterial pressure (from 97 +/- 6 to 74 +/- 6 mm Hg; P less than 0.05). No changes in arterial pressure were observed in the three groups of control rats. These findings indicate that endogenous vasopressin is as important as angiotensin II in the maintenance of arterial pressure in cirrhotic rats with ascites and support the contention that arterial hypotension is the initial event leading to the stimulation of the renin-angiotensin system and vasopressin in this animal model of cirrhosis.
...
PMID:Effect of V1-vasopressin receptor blockade on arterial pressure in conscious rats with cirrhosis and ascites. 182 29

The natriuretic effect of pharmacological doses of atrial natriuretic peptide (ANP) is markedly reduced in cirrhosis with ascites. The current study, which includes two protocols, was carried out to investigate whether this phenomenon is related to the altered systemic hemodynamics present in cirrhosis. In protocol A, the administration of ANP (2.5 micrograms.kg-1 as a bolus followed by a constant infusion of 0.1 microgram.kg-1.min-1) to 10 rats with carbon tetrachloride-induced cirrhosis and ascites produced a significantly lower increase in diuresis (13.4 +/- 1.3 microliters/min) and natriuresis (2.3 +/- 0.3 mu Equiv/min) than in 10 control rats (56.3 +/- 1.4 microliters/min and 8.7 +/- 0.5 mu Equiv/min, respectively), indicating a renal resistance to the effect of ANP in this experimental model of cirrhosis. The reduction of arterial pressure induced by ANP was similar in both groups. However, since baseline mean arterial pressure was significantly lower in cirrhotic rats, the degree of hypotension during ANP infusion was also greater in this group of animals (82 +/- 3 vs. 109 +/- 2 mmHg). The aim of protocol B was to assess whether normalization of arterial pressure in cirrhotic rats increases the renal response to ANP. This protocol includes two groups of 10 rats with cirrhosis and ascites infused with a glucose solution containing norepinephrine (CT-NE rats) or angiotensin II (CT-AII rats) at doses to normalize arterial pressure and an additional control group of 10 cirrhotic rats with ascites receiving only glucose solution (CT rats). Angiotensin II, but not norepinephrine or glucose solution administration, was associated with a significant increase in urine volume and sodium excretion. During ANP infusion, CT rats showed a blunted diuretic and natriuretic response. In contrast, the ANP-induced increase in urine volume and sodium excretion observed in CT-NE (53.6 +/- 10.4 microliters/min and 9.3 +/- 2.2 mu Equiv/min) and CT-AII rats (98.3 +/- 11.6 microliters/min and 15.5 +/- 2.9 mu Equiv/m), was similar or even greater than that showed by the healthy rats of protocol A. The degree of hypotension during ANP administration was also similar (CT-NE, 104 +/- 2; CT-AII, 108 +/- 5 mmHg). These results suggest that the blunted response to pharmacological doses of ANP in cirrhosis with ascites is related to altered systemic hemodynamics of cirrhosis, which further deteriorates during the infusion of the peptide.
...
PMID:Role of altered systemic hemodynamics in the blunted renal response to atrial natriuretic peptide in rats with cirrhosis and ascites. 253 Feb 68

The hepatic perfusion index (HPI) may be of value in the diagnosis of liver micro-metastases. However, raised values of HPI also occur in some benign liver conditions (e.g. cirrhosis), thereby weakening the diagnostic power of this test. It has been suggested that infusion of the vaso-active agent angiotensin II might improve the predictive value of dynamic scintigraphy because it has been shown to alter liver perfusion in patients with metastatic liver disease. Basal HPI values were not significantly different in a group of patients with metastases (n = 10) and a group with cirrhosis (n = 9). A significant rise in HPI occurred in the metastatic group using angiotensin II enhancement (p less than 0.01, Wilcoxon test). In the cirrhotic group there was no significant increase in the HPI with angiotensin II enhancement. Within the groups, there was considerable variation in response, with eight of ten metastatic and five of nine cirrhotic patients showing a rise in HPI during an angiotensin II infusion. As a result, there was complete overlap in the angiotensin II enhanced HPI for the two groups. Angiotensin II enhancement of HPI is therefore unlikely to improve the diagnostic power of dynamic scintigraphy in individual patients with established hepatic disease.
...
PMID:Clinical evaluation of angiotensin II enhanced perfusion scintigraphy in metastatic liver disease. 281 38

The ability of the kidneys to excrete sodium and free water is often impaired in patients with cirrhosis. Sodium retention is a sine qua non for ascites formation. The impairment of water excretion causes hyponatremia and hypo-osmolality. In addition, these patients frequently have functional renal failure caused by intense renal vasoconstriction. The renin-angiotensin-aldosterone system and the sympathetic nervous system, which are activated in most cirrhotic patients with ascites, and a nonosmotic hypersecretion of antidiuretic hormone are important mechanisms of sodium and water retention. Angiotensin II and sympathetic nervous activity may also be involved in the pathogenesis of functional renal failure. The renal production of prostaglandins is increased in cirrhotic patients with ascites as a homeostatic response to antagonize the vascular effect of endogenous vasoconstrictors and the tubular action of antidiuretic hormone. Nonsteroidal anti-inflammatory drugs should, therefore, be administered with caution in these patients because they may induce acute renal failure and water retention. Although sulindac inhibits the renal synthesis of prostaglandins in cirrhotic patients with ascites, it appears to have less effect on renal function than do other nonsteroidal anti-inflammatory drugs administered to these patients.
...
PMID:Renal function abnormalities, prostaglandins, and effects of nonsteroidal anti-inflammatory drugs in cirrhosis with ascites. An overview with emphasis on pathogenesis. 294 81

The available evidence suggests that angiotensin plays an important role in sodium homeostasis not only via aldosterone release but also through control of the renal circulation, and thereby renal sodium handling. Perhaps this intrarenal action is the renin-angiotensin system's original, primitive function. Through its vascular action, angiotensin has an important influence on glomerular filtration and tubular reabsorption. Angiotensin almost certainly also has an additional intraglomerular action. More circumstantial, but compelling, evidence suggests that angiotensin contributes to the renal response in a host of conditions characterized by renal vasoconstriction, a reduction in filtration rate, and sodium retention, including heart failure, cirrhosis of the liver, complications of pregnancy, the renal response to trauma and shock, and in selected patients with essential and secondary hypertension. Pharmacologic interruption of the renin-angiotensin system is proving useful not only for blood pressure control in patients with hypertension but also because of its influence on the kidney in some or all of these conditions--at least in part attributable to restoration of more normal renal sodium handling.
...
PMID:The renin-angiotensin system and sodium homeostasis. 620 38

We have studied the effect of angiotensin-II blockade with saralasin on the cardiovascular and hepatic hemodynamics and on the renin-angiotensin-aldosterone system in fourteen patients with cirrhosis and ascites. Control measurements showed that most of the patients had a low mean arterial pressure, high plasma volume, normal or high cardiac index, low peripheral resistance and high plasma renin activity and aldosterone concentration. The wedged hepatic venous pressure was increased in each patient and the estimated hepatic blood flow was normal in most of them. Overall, saralasin induced a significant reduction of the mean arterial pressure, cardiac index and peripheral resistance. The decrease of the peripheral resistance was greater than that of the cardiac index. Six of the patients developed a marked reduction of the mean arterial pressure with low doses of saralasin (1--2.5 microgram/kg/min), and they had significantly higher plasma renin activity and lower mean arterial pressure than the remaining eight patients who showed a slight or no hypotensive response in spite of infusing saralasin up to a dose of 10 micrograms/kg/min. Overall, the decrease of the mean arterial pressure correlated directly with the baseline values of plasma renin activity. Angiotensin-II blockade induced a significant reduction of the wedged hepatic venous pressure. The hepatic blood flow did not show any significant change. The decrease of the wedged hepatic venous pressure was directly related to the reduction of the mean arterial pressure and also to the control plasma renin activity. Our study indicates that in most patients with cirrhosis, ascites and high plasma renin activity, arterial pressure is maintained by the effect of endogenous angiotensin II on the peripheral vasculature, and we suggest that a pre-existing arterial hypotension secondary to an arteriolar vasodilatation is the cause of renin release in these patients. Our results also show that angiotensin-II blockade is accompanied by a reduction of the post-sinusoidal hepatic vascular resistance.
...
PMID:Effect of angiotensin-II blockade on systemic and hepatic haemodynamics and on the renin-angiotensin-aldosterone system in cirrhosis with ascites. 679 42

The pharmacokinetics of furosemide (frusemide) in patients with oedema have been relatively well studied, but in many studies it is unclear whether the disease or the oedema per se has the major effect. The rate of absorption of oral furosemide in patients with oedema was decreased, but total bioavailability was almost unchanged. The peak serum concentration (Cmax) and time taken to achieve Cmax were either decreased or unchanged. Binding of furosemide to plasma proteins is lower in patients with congestive heart failure (CHF), decompensated liver cirrhosis (DLC) and nephrotic syndrome, probably as a result of hypoalbuminaemia. The elimination half-life (t1/2) can be unchanged (CHF, DLC) or prolonged (chronic renal failure: CRF). Plasma and renal clearance are reduced in patients with CRF and nephrotic syndrome, but are almost unchanged in CHF and DLC. Disease-induced disorders are mainly responsible for the alterations of furosemide pharmacokinetics in oedematous conditions, while the influence of oedema per se is probably not clinically relevant. The pharmacokinetics of digoxin have been studied in a small number of studies only. In patients with CHF, considerable interindividual differences have been found. Because digoxin has a narrow therapeutic window, this drug should be administered cautiously to oedematous patients. Theophylline has higher bioavailability in patients with oedema, with a significantly higher Cmax in patients with hepatic cirrhosis and CHF than in healthy volunteers (29 and 22%, respectively). Furthermore, clearance decreases and t1/2 increases in these patients. Angiotensin converting enzyme (ACE) inhibitors are often administered as prodrugs, and their pharmacokinetic profile could be influenced by the diseases that accompany oedematous states. However, the effect of oedema is difficult to discriminate from that of the disease. Individual ACE inhibitors are affected differently, but importantly the dosage of perindopril should be reduced in patients with CHF, while for most other ACE inhibitors the changes in pharmacokinetic parameters are clinically irrelevant. In conclusion, studies on pharmacokinetic changes in oedema are limited. Besides affecting absorption (after oral administration) and conversion of the prodrug to the active form, probably as a result of the associated disease, oedema has not been proven to cause any clinically relevant changes in pharmacokinetic parameters for individual drugs. However, further studies of this aspect of pharmacokinetics are needed.
...
PMID:Pharmacokinetic changes in patients with oedema. 761 78

A decreased pressor response to endogenous vasoconstrictors, such as angiotensin II and vasopressin, is a characteristic finding in cirrhosis with ascites; this has been considered as partially responsible for the arteriolar vasodilation present in this disease. Previous investigations suggested that this abnormality is due to a post-receptor defect leading to altered intracellular Ca2+ mobilization. To assess this hypothesis, vascular responsiveness to angiotensin II (3.10(-8) M) and intracellular Ca2+ concentration in basal conditions and following angiotensin II (1-100 nM) and vasopressin stimulation (100 nM) were measured in aortic rings and in primary cultured aortic vascular smooth muscle cells, respectively. The study was carried out in 43 control rats and 40 rats with CCl4-induced cirrhosis and ascites. Cells were grown to confluence on glass cover slips and then loaded with Fura-2, a fluorescent intracellular Ca2+ indicator, for continuous monitoring of intracellular Ca2+ concentration. A decreased constrictor response to angiotensin II was detected in cirrhotic aortic rings in comparison to control rings (increase in tension: 31 +/- 5 vs 79 +/- 14 mg, p < 0.005). No differences in intracellular Ca2+ concentration between cirrhotic and control cells were observed in basal conditions (104 +/- 6 and 100 +/- 3 nM, respectively). Angiotensin II administration to cirrhotic vascular smooth muscle cells had a dose-dependent biphasic effect consisting of a rapid increase, followed by return to a sustained level significantly higher than the basal value. This response was identical to that observed in control vascular smooth muscle cells. Similar findings were obtained following vasopressin stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Intracellular calcium concentration in vascular smooth muscle cells of rats with cirrhosis. 781 97

In order to elucidate a participation of intact parathyroid hormone (PTH(1-84)) in blood pressure (BP) and body fluid homeostasis, we studied fluctuations of PTH(1-84) during manipulations of BP in hyperparathyroid and healthy subjects, and during manipulations of blood volume in patients with glomerulonephritis or liver cirrhosis and in controls. Angiotensin II induced BP elevation was associated with increased values of PTH(1-84) both in healthy subjects (12-25 ng l-1, medians, p < 0.01), in patients with primary hyperparathyroidism (94-125 ng l-1, p < 0.01), in patients with low calcium due to end stage renal disease before requirement of dialysis (95-151 ng l-1, p < 0.02), and in patients with tertiary hyperparathyroidism (221-264 ng l-1, p < 0.05), but not in dialysis patients without hypercalcaemia (126-174 ng l-1, NS). The changes could not be attributed to reduction of serum calcium, but probably to the increase of plasma angiotensin II, which was positively correlated to the increase of serum PTH(1-84) in the healthy subjects (p = 0.619, n = 15, p < 0.05) and in the patients with primary hyperparathyroidism (p = 0.549, n = 18, p < 0.05). Noradrenaline induced BP elevation did not have a similar effect on PTH(1-84), and changes of PTH(1-84) were not related to changes of BP. Volume depletion after furosemide injection, also accompanied by increased levels of angiotensin II, resulted in elevation of PTH(1-84) in controls, cirrhotics, patients with glomerulonephritis without the nephrotic syndrome, but not in nephrotic patients. Volume depletion induced by bolus injection of atrial natriuretic peptide (ANP) was associated with decreased PTH(1-84) in healthy subjects (20-18 ng l-1, p < 0.02), but not in patients with nephrotic syndrome and liver cirrhosis. Volume expansion induced by albumin infusion caused increased plasma levels of ANP, but PTH(1-84) was unaltered. Thus, angiotensin II may be able to stimulate, and ANP to inhibit release of PTH(1-84), and PTH(1-84) may be involved in the regulation of BP and body fluid homeostasis. BP changes or changes in blood volume per se do not seem to influence PTH(1-84) levels.
...
PMID:Parathyroid hormone in blood pressure and volume homeostasis in healthy subjects, hyperparathyroidism, liver cirrhosis and glomerulonephritis. A possible interaction with angiotensin II and atrial natriuretic peptide. 786 30

Resistance to the natriuretic action of atrial natriuretic factor (ANF) in cirrhosis with ascites has been correlated with rising levels of antinatriuretic factors, such as renin, angiotensin II (AII), and aldosterone, as well as increased sympathetic nerve activity. To determine whether AII can serve as a mediator rather than only as a marker of the antinatriuresis, a nonpressor dose of AII (5 ng/kg/min) was given during an ANF infusion in eight patients with cirrhosis and ascites who responded to ANF infusion with a natriuresis. Patients were maintained in metabolic balance and measurements of para-aminohippuric acid, inulin, and lithium clearance were taken before and during infusion of ANF with or without AII. Atrial natriuretic factor infusion was associated with a natriuretic response accompanied by an increase in glomerular filtration rate, filtration fraction, and lithium clearance compared with baseline. The addition of AII was associated with a return of the glomerular filtration rate to baseline, with no change in filtration fraction. This was reversible on withdrawal of AII infusion. Natriuresis induced by ANF occurred despite baseline elevations of the renin angiotensin aldosterone system and was associated with an increase in distal delivery of sodium and a decrease in fractional reabsorption of distally delivered sodium as estimated by lithium clearance parameters. Angiotensin II infusion exerted effects on both proximal and distal nephron sites to abrogate ANF-induced natriuresis. These results suggest that AII may serve as a mediator as well as a marker of resistance to the natriuretic effect of ANF in patients with cirrhosis and ascites.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Angiotensin II modulates atrial natriuretic factor-induced natriuresis in cirrhosis with ascites. 848 14

1 2 3 Next >>