Search PubMed⌕ Search

Biomedical subjects

J Gaya

Publications and source records attributed to J Gaya.

At least 37 records · Page 2Linked to original sources
PubMed1991

Temporal relationship between the decrease in arterial pressure and sodium retention in conscious spontaneously hypertensive rats with carbon tetrachloride-induced cirrhosis.

It has been proposed that the initial event of sodium retention in cirrhosis is a peripheral arteriolar vasodilation causing underfilling of the arterial vascular compartment and stimulation of the renin-aldosterone and sympathetic nervous systems. To test this hypothesis, systolic blood pressure, sodium balance and urinary excretion of sodium and aldosterone were sequentially measured in 13 conscious spontaneously hypertensive rats submitted to a cirrhosis induction program with carbon tetrachloride and phenobarbital and in 14 control hypertensive animals. No significant differences were found between control and cirrhotic rats in any of the measured parameters during the first 7 wk of the study. The eighth week sodium retention developed in cirrhotic rats as indicated by a positive sodium balance and a marked decrease of sodium excretion. At the same time a significant reduction in systolic blood pressure and a great increase in urinary excretion of aldosterone were detected. These changes were more marked the ninth week of the study. In cirrhotic rats there was a highly significant direct correlation between systolic blood pressure and urinary sodium excretion. Postmortem examination showed a histological picture of cirrhosis in all animals given carbon tetrachloride and ascites in six of them. These results indicate that the onset of hyperaldosteronism and sodium retention in conscious spontaneously hypertensive rats with carbon tetrachloride-induced cirrhosis is chronologically related to a significant decrease in arterial pressure, thus supporting the "peripheral arterial vasodilation hypothesis" of ascites.

Aldosterone↗
PubMed1990

Effects of intravenous amino acid infusion and dietary proteins on kidney function in cirrhosis.

Acute intravenous amino acid infusion or a high-protein diet increases renal plasma flow and the glomerular filtration rate in healthy subjects. Conversely, a low-protein diet reduces renal plasma flow and glomerular filtration rate. The aim of this study was to investigate the effect of intravenous amino acid infusion and dietary proteins on kidney function in cirrhosis. Protocol 1: renal plasma flow and glomerular filtration rate were measured before and during intravenous administration of a 10% amino acid solution (0.043 ml/kg/min) to eight compensated cirrhotic patients (group 1), nine nonazotemic cirrhotic patients with ascites (group 2) and seven cirrhotic patients with ascites and functional renal failure (group 3). Amino acid administration induced a significant increase in renal plasma flow and glomerular filtration rate in all groups studied. Renal plasma flow and glomerular filtration rate increased by 16% and 14%, respectively, in group 1; 31% and 22% in group 2 and 25% and 21% in group 3. Protocol 2: Renal plasma flow and glomerular filtration rate were measured in nine cirrhotic patients with ascites after 11 days on a low-protein diet (0.5 gm/kg body weight/day) and also after the patients followed for 11 days a moderately high-protein diet (1.5 gm/kg body weight/day). The moderately high-protein diet was associated with a significant increase in renal plasma flow (12%) and glomerular filtration rate (13%) compared with values obtained while the patients followed the low-protein diet. Plasma glucagon levels increased markedly during the intravenous administration of amino acid and the intake of the moderately high-protein diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1990

Natriuretic hormone activity in the urine of cirrhotic patients.

The ability of urine extracts to inhibit sodium and potassium-activated ATPase, cross-react with antidigoxin antibodies and induce natriuresis in rats was investigated in 10 healthy subjects, 10 cirrhotic patients without ascites (compensated cirrhotics), 27 nonazotemic cirrhotic patients with ascites and 10 cirrhotic patients with ascites and functional renal failure to assess whether reduced activity of natriuretic hormone contributes to sodium retention in cirrhosis. No significant differences were seen between healthy subjects and compensated cirrhotic patients in any of these parameters (sodium and potassium-activated ATPase inhibition = 178.5 +/- 19.8 vs. 247.4 +/- 48.7 nmol equivalent of ouabain/day; digoxinlike activity = 43.9 +/- 6.1 vs. 48.0 +/- 5.6 ng equivalent of digoxin/day; natriuretic activity = 0.36 +/- 0.15 vs. 0.63 +/- 0.27 mumol/min). Cirrhotic patients with ascites with and without functional renal failure showed significantly higher values of sodium and potassium-activated ATPase inhibition (708.1 +/- 94.0 and 529.2 +/- 53.9 nmol equivalent of ouabain/day, respectively), digoxinlike activity (136.9 +/- 7.2 and 116.3 +/- 7.9 ng equivalent of digoxin/day) and natriuretic activity (1.78 +/- 0.48 and 1.93 +/- 0.37 mumol/min) than healthy subjects and compensated cirrhotic patients. We saw no significant differences between these two groups of cirrhotic patients with ascites with respect to these parameters. In the cirrhotic patients studied, sodium and potassium-activated ATPase inhibition and antidigoxin antibodies directly correlated with the degree of impairment of hepatic and renal function, plasma renin activity and plasma levels of aldosterone and norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effects of thromboxane synthesis inhibitor triflusal on renal hemodynamics in microalbuminuric diabetic patients.

Triflusal (2-acetoxy-4-trifluormethylbenzoic acid) is a platelet-antiaggregant drug that selectively inhibits thromboxane synthesis with little effect on prostacyclin production. In this study, we evaluated the effect of 5-day administration of 900 mg/day triflusal on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary albumin excretion (UAE), thromboxane B2 (TXB2), 6-ketoprostaglandin F1 alpha (PGF1 alpha), and PGE2 in nine normotensive insulin-dependent diabetic patients with UAE between 30 and 103 micrograms/min. Plasma TXB2 and plasma renin activity (PRA) were also determined. After administration of triflusal, we observed a reduction in microalbuminuria (59 +/- 25 vs. 33 +/- 22 micrograms/min, P less than 0.01), an increase in RPF (648 +/- 119 vs. 722 +/- 134 ml.min-1 x 1.73 m-2, P less than 0.01), and a reduction in filtration fraction (0.24 +/- 0.04 vs. 0.20 +/- 0.03, P less than 0.01). Triflusal produced a significant reduction in both plasma TXB2 (130 +/- 39 vs. 52 +/- 32 pg/ml, P less than 0.02) and urine TXB2 (523 +/- 249 vs. 312 +/- 11 pg/min, P less than 0.02), without changes in PRA and UAE of 6-keto-PGF1 alpha and PGE2. Metabolic control and arterial blood pressure did not change during the study. These results suggest that platelet-antiaggregant therapy can reduce microalbuminuria in diabetic patients. This effect could be mediated by a reduction in the transglomerular hydraulic pressure through a vasodilation of efferent arterioles secondary to renal thromboxane synthesis inhibition.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Urinary excretion of endogenous digitalis-like natriuretic substances in healthy subjects. Effect of sodium load.

In the current study digoxin-like immunoreactivity (DLIA), Na-K-ATPase inhibition and natriuretic activity of urinary extracts from 10 healthy volunteers following a low and a high-sodium intake, respectively, were measured. Detectable urinary DLIA (46.1 +/- 5.6 ng eq digoxin/day), Na-K-ATPase inhibition (182.9 +/- 22.7 nmol eq oub/day) and natriuretic activity (UNaV: 0.38 +/- 0.11 microEq/min) were observed during the low-sodium diet period in all subjects. High-sodium diet was associated with a significant increase in DLIA (87.9 +/- 9.2 ng eq digoxin/day, p less than 0.001) which parallelled changes in Na-K-ATPase inhibition (359.8 +/- 51.9 nmol eq oub/day, p less than 0.005) and natriuretic activity (UNaV: 1.33 +/- 0.3 microEq/min, p less than 0.025). These results support the contention that DLIA is related to NH.

Adult↗
PubMed1990

Increased gastric PGE2 biosynthesis in cirrhotic patients with gastric vascular ectasia.

Plasma levels of glucagon, secretin, norepinephrine, arginine-vasopressin, and prostaglandin biosynthesis in the gastric mucosa were determined in cirrhotic patients with gastric vascular ectasia associated with hypoacidity, in cirrhotics without this lesion, and in healthy controls. Plasma concentrations of glucagon, secretin, and norepinephrine were similar in cirrhotics with gastric vascular ectasia and cirrhotics without this lesion, these concentrations being significantly higher (p less than 0.05) than in healthy controls. However, there was no significant difference between plasma levels of arginine-vasopressin in patients with cirrhosis (with or without gastric vascular ectasia) and those in healthy controls. The biosynthesis of prostaglandin E2 in the antrum of the gastric mucosa was significantly higher in cirrhotics with gastric vascular ectasia than in cirrhotics without this lesion (p less than 0.05) and healthy controls (p less than 0.005). Prostaglandin E2 in the corpus was significantly higher (p less than 0.05) in cirrhotics with gastric vascular ectasia than in healthy controls. The biosynthesis of 6-keto PGF1 alpha (a stable metabolite of prostacyclin) and PGF2 alpha in the corpus and antrum of gastric mucosa was not significantly different in cirrhotics with gastric vascular ectasia, cirrhotics without this lesion and healthy controls. Since prostaglandin E2 has a vasodilator and acid-inhibitory effect, we speculate that high content of this prostanoid in the gastric mucosa may play a role in the pathogenesis of ectatic capillaries and acid inhibition present in some cirrhotic patients.

Adult↗
PubMed1989

Effects of atrial natriuretic peptide on urinary kallikrein excretion and renal function in rats.

We investigated whether the renal kallikrein-kinin system is involved in the renal effects of atrial natriuretic peptide (ANP) by measuring the glomerular filtration rate (GFR), urine volume (UV) and urinary excretion of sodium (UNaV) and kallikrein (UkkV) in 4 groups of 10 anesthetized rats before and during (two 10 min periods) the i.v. infusion of Ringer solution (control group) or different doses of ANP (0.25, 0.5 and 1 microgram, respectively). The administration of ANP was associated with a marked and significant increase in UV, UNaV, UkkV and GFR. The diuretic and natriuretic responses to ANP were dose-related, while the changes in GFR and UkkV were short-lived and not related to the dose of ANP. There was no relationship between UV or UNaV and UkkV after ANP administration. In contrast, UkkV correlated closely with GFR (r = 0.675, P less than 0.001). These data do not support the hypothesis that the kallikrein-kinin system contributes to the diuretic and natriuretic effects of ANP, but it might be involved in the renal hemodynamic action of this peptide.

Animals↗
PubMed1989

Role of altered systemic hemodynamics in the blunted renal response to atrial natriuretic peptide in rats with cirrhosis and ascites.

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.

Angiotensin II↗
PubMed1989

Lymphocyte beta 2-adrenergic receptors in essential hypertension: studies in basal conditions and after dynamic exercise.

In order to study the density and response to dynamic exercise of lymphocyte beta 2-adrenoceptors in essential hypertension, 30 moderate essential hypertensives (12 men: 18 women, mean age 50.3 +/- 9.2 years) and 14 normotensive controls (8 men: 7 women, mean age 47 +/- 15 years) were studied. Beta 2-adrenoceptors density in basal conditions was higher in essential hypertensives than in controls (1950 +/- 625 vs 1278 +/- 356 binding sites per cell [bs/c], respectively, p less than 0.01) (mean +/- SD). After dynamic exercise beta 2-adrenoceptors density increased both in controls (to 1491 +/- 342 bs/c, p less than 0.01) and in hypertensives (to 2632 +/- 715 bs/c, p less than 0.001). However, the percentage of increase after the exercise was significantly higher in hypertensives than in controls (40.5 +/- 6.1 vs 20.2 +/- 6.5%, p less than 0.05). In summary, the higher density in basal conditions, as well as the exaggerated increase in the number of beta 2-adrenoceptors after dynamic exercise observed in essential hypertension, suggest an impaired regulation of these receptors in essential hypertension.

Adult↗
PubMed1988

Prognostic value of arterial pressure, endogenous vasoactive systems, and renal function in cirrhotic patients admitted to the hospital for the treatment of ascites.

To identify prognostic factors in cirrhotic patients admitted to the hospital for the treatment of an episode of ascites, a survival analysis was performed in a series of 139 patients hospitalized in our Unit between 1980 and 1985. Mean follow-up was 12.8 +/- 14.2 mo (mean +/- SD). A total of 38 variables based on history, physical examination, hepatic biochemical tests, renal function tests, and endogenous vasoactive systems were analyzed for prognostic value. Eighteen of these variables had prognostic value in the univariate analysis. A multivariate analysis (Cox's regression method) disclosed that 7 of these 18 variables had independent prognostic value. Of these independent predictors of survival, mean arterial pressure and plasma norepinephrine concentration were the variables that best predicted prognosis. Two other variables that independently correlated with survival were urinary sodium excretion and glomerular filtration rate. The remaining three independent predictors of survival were nutritional status, hepatomegaly, and serum albumin concentration. Therefore, these findings indicate that, in patients with cirrhosis and ascites, parameters estimating systemic hemodynamics and renal function are better predictors of survival than those routinely used to estimate hepatic function.

Adult↗
PubMed1988

Prostaglandin precursor fatty acids in cirrhosis with ascites: effect of linoleic acid infusion in functional renal failure.

1. Functional renal failure (FRF) in cirrhosis with ascites could be related to an inappropriately low renal prostaglandin (PG) production. To investigate whether the impaired renal PG synthesis in these patients is related to a PG precursor fatty acid deficiency, serum levels of linoleic and arachidonic acids and the urinary excretion of PGE2, 6-keto-PGF1 alpha and thromboxane B2 (TxB2) were measured in 10 normal subjects, 17 non-azotaemic cirrhotic patients with ascites and 10 cirrhotic patients with ascites and FRF. 2. Serum linoleic acid levels were similar in the three groups studied. Both groups of cirrhotic patients showed lower arachidonic acid levels than normal subjects; however, non-azotaemic cirrhotic patients and patients with FRF did not differ in relation to serum arachidonic acid. 3. Non-azotaemic cirrhotic patients had higher urinary PGE2, 6-keto-PGF1 alpha and TxB2 excretion than normal subjects and cirrhotic patients with FRF. Patients with FRF showed similar urinary PGE2 and TxB2 and lower urinary 6-keto-PGF1 alpha than normal subjects. In all cirrhotic patients no significant correlation was found between serum linoleic and arachidonic acid levels and urinary PGs. 4. In seven patients with FRF an acute intravenous infusion of linoleic acid induced a marked increase in serum levels of this fatty acid. However, no increase in serum arachidonic acid levels and urinary PG excretion and no improvement in renal function was observed. 5. This study suggests that an arachidonic acid deficiency is present in cirrhotic patients with ascites but that this abnormality is not a major determinant of renal function and PG production in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Longitudinal study of renal prostaglandin excretion in cirrhotic rats: relationship with the renin-aldosterone system.

1. A cross-sectional study (protocol A) was performed in 19 rats with cirrhosis, induced by carbon tetrachloride (CCl4), and ascites and in 10 control animals to assess renal prostaglandin (PG) excretion in experimental cirrhosis. In an additional group of animals, including nine rats chronically exposed to CCl4 (CCl4 rats) and six control rats, a longitudinal study (protocol B) was performed to investigate the temporal relationship between changes in renal PG excretion, the renin--aldosterone system and renal function. 2. Urinary PG excretion was assessed by specific radioimmunoassay of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane (TX) B2 after extraction with octadecyl silica cartridges and h.p.l.c. purification. Recoveries for each prostanoid (61 +/- 8% for PGE2, 64 +/- 12% for PGF2 alpha, 65 +/- 11% for 6-keto-PGF1 alpha and 66 +/- 17% for TXB2) were determined in every sample by adding tritiated standards, and the final values were corrected according to the individual recoveries. 3. Cirrhotic rats with ascites in protocol A showed a significantly higher plasma renin and aldosterone concentrations and urinary excretion of 6-keto-PGF1 alpha and TXB2 than did control animals. Urinary excretion of PGE2 and PGF2 alpha, however, was significantly reduced in cirrhotic animals as compared with controls. 4. In CCl4 rats included in protocol B, there was a close chronological relationship between the activation of the renin-aldosterone system, as estimated by urinary aldosterone excretion, the onset of sodium retention and the increase in urinary excretion of 6-keto-PGF1 alpha and TXB2. The urinary excretion of PGE2 and PGF2 alpha in CCl4 rats was reduced throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Effect of atrial natriuretic peptide on arterial pressure and renal function in cirrhotic rats with ascites.

Glomerular filtration rate, urine volume, sodium excretion and mean arterial pressure were measured in 10 rats with Cl4C induced cirrhosis presenting sodium retention and ascites, and in 10 control rats before and during the iv administration of the 28 aminoacid rat alpha-Atrial Natriuretic Peptide (alpha-ANP) (a bolus of 1 microgram followed by a constant infusion of 33 ng/min). alpha-ANP induced a similar increase in glomerular filtration rate and filtered sodium load in both groups of rats. In contrast, the increase in urine volume and sodium excretion produced by alpha-ANP was significantly lower in cirrhotic rats (from 13.8 +/- 1.9 to 37.9 +/- 9.1 microliters/min., and from 0.5 +/- 0.1 to 3.3 +/- 1.0 microEq/min) than in control animals (from 14.6 +/- 1.3 to 102.5 +/- 17.7 microliters/min., p less than 0.005; and from 1.0 +/- 0.3 to 14.1 +/- 3.2 microEq/min., p less than 0.001). The results indicate that in rats with experimental cirrhosis and ascites there are blunted diuretic and natriuretic responses to alpha-ANP, probably as a consequence of the exaggerated tubular sodium reabsorption present in these animals.

Animals↗
PubMed1988

Effect of spironolactone on the renin-aldosterone system in rats.

PRA, PRC and the plasma concentration of aldosterone (Aldo) were measured in rats (Sp-rats) receiving a daily sc injection of Spironolactone, (Sp, 20 mg in olive oil) and in control rats (C-rats) receiving olive oil only. Animals were studied one day after starting treatment, 5 days on treatment or after 5 weeks on the study. PRA, PRC and Aldo were significantly increased in Sp-rats as compared to C-rats throughout all the study. In additional Sp-rats and C-rats, the urine volume, serum Na+ and K+ concentration, Na+ and K+ intake and the urinary excretion of Na+, K+ and aldosterone-18-glucuronide (UAldV) were serially measured during 5 weeks. The total radioactivity plasma clearance after an i.v. bolus injection of 3H-aldosterone was subsequently measured in (5 Sp-rats and 5 C-rats). No significant differences in serum Na+ and K+ concentration and in Na+ and K+ balance were observed between Sp-rats and C-rats. UAldV was significantly higher in Sp-rats than in C-rats during all the study. After 5 weeks on treatment the total radioactivity plasma clearance was significantly higher in Sp-rats than in C-rats. These results indicate that Sp, at high dosage, stimulates renin release and aldosterone secretion by a mechanism unrelated to alterations in Na+ and K+ balance.

Aldosterone↗
PubMed1987

Temporal relationship between the impairment of free water excretion and antidiuretic hormone hypersecretion in rats with experimental cirrhosis.

To investigate the temporal relationship between the impairment of water excretion, sodium retention, and antidiuretic hormone hypersecretion in cirrhosis, free water excretion (estimated by the minimum urinary osmolality) and urinary antidiuretic hormone excretion (which correlates with the plasma levels of this hormone) were measured weekly after an oral water load in 18 rats with carbon tetrachloride-induced cirrhosis and in 20 control animals. The onset of ascites (as an index of sodium retention) in cirrhotic rats was estimated by sequential paracentesis. Thirteen cirrhotic animals developed an impairment of water excretion 2-5 wk after the onset of ascites. The urinary excretion of antidiuretic hormone in these animals, which was normal before the impairment of water excretion, increased markedly within the week in which this abnormality was first detected and remained high thereafter. The remaining 5 cirrhotic rats did not experience an impairment of free water excretion in spite of developing ascites. The urinary excretion of antidiuretic hormone in these animals was similar to that of control rats during the entire study. In all urine samples obtained from cirrhotic rats, there was a highly significant direct linear correlation between the urinary excretion of antidiuretic hormone and the minimum urinary osmolality. Our results show the following: in rats with carbon tetrachloride-induced cirrhosis, sodium retention preceded the impairment of water excretion; and in these animals, the defect in water metabolism correlated chronologically and quantitatively with antidiuretic hormone hypersecretion. These findings are consistent with the concept that antidiuretic hormone is a major determinant of the impaired water metabolism in cirrhosis.

Animals↗
PubMed1986

Renal function abnormalities, prostaglandins, and effects of nonsteroidal anti-inflammatory drugs in cirrhosis with ascites. An overview with emphasis on pathogenesis.

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.

Anti-Inflammatory Agents↗