Biomedical subjects

J Clària

Publications and source records attributed to J Clària.

6 recordsLinked to original sources

PubMed1992

Pathogenesis of arterial hypotension in cirrhotic rats with ascites: role of endogenous nitric oxide.

Nitric oxide is a vasodilator tonically secreted by endothelial cells that is involved in the regulation of arteriolar tone. This study, which includes two protocols, was performed to investigate whether nitric oxide plays a role in the pathogenesis of arterial hypotension in cirrhosis with ascites. In protocol 1, the administration of increasing doses (25, 50, 250, 500 and 1,000 micrograms.kg-1.min-1) of the nitric oxide biosynthesis inhibitor N omega-nitro-L-arginine to 18 conscious rats with cirrhosis and ascites produced, at each dose tested, a significantly greater increase in arterial pressure than in 17 conscious control rats. At the lowest dose of N omega-nitro-L-arginine, arterial pressure significantly rose in cirrhotic rats but not in controls. In protocol 2, arterial pressure, estimated renal plasma flow, glomerular filtration rate and sodium excretion were measured in 12 cirrhotic rats with ascites and 10 control rats before and during the sequential infusion of previously selected doses of N omega-nitro-L-arginine (25, 50 and 250 micrograms.kg-1.min-1). Changes in arterial pressure reproduced those observed in protocol 1. In control rats, N omega-nitro-L-arginine caused a decrease in estimated renal plasma flow without affecting glomerular filtration rate or sodium excretion. In contrast, N omega-nitro-L-arginine administration to cirrhotic animals did not produce any appreciable renal vasoconstrictor effect, and it increased glomerular filtration rate and sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Effects of somatostatin on renal function in cirrhosis.

To investigate the renal effects of somatostatin in cirrhosis, renal function and plasma and urinary levels of endogenous neurohumoral vasoactive substances were measured in conditions of intravenous water overload (20 mL/kg body wt with 5% glucose) before and during the intravenous infusion of somatostatin (250-500 micrograms/h) in 6 cirrhotic patients without ascites and 17 nonazotemic cirrhotic patients with ascites. Somatostatin induced a significant reduction of renal plasma flow, glomerular filtration rate, and free water clearance in both groups of patients. In patients with ascites, somatostatin also reduced urinary sodium excretion. Changes in renal function were significantly more marked in patients with ascites than in those without ascites and occurred in the absence of changes in mean arterial pressure and plasma levels of renin, aldosterone, norepinephrine, antidiuretic hormone, and atrial natriuretic peptide. Somatostatin induced a significant reduction in the plasma concentration of glucagon and urinary excretion of prostaglandin E2 that was not related to changes in renal function. These findings indicate that somatostatin administration induces renal vasoconstriction and impairs glomerular filtration rate, free water clearance, and sodium excretion in cirrhosis by a mechanism unrelated to systemic hemodynamics and endogenous neurohumoral vasoactive systems.

Dinoprostone↗

PubMed1991

Doses of endothelin have natriuretic effects in conscious rats with cirrhosis and ascites.

MAP, RPF, GFR, V and UNaV were measured in nine conscious control and in 11 conscious cirrhotic rats with ascites before and following two bolus injections (100 and 600 pmol/kg body wt) of endothelin (ET). PRA and plasma concentration of aldosterone and ANP were measured in basal conditions and following the high dose ET. ET induced similar increase in MAP and decrease in RPF and GFR in control and cirrhotic rats. High-dose ET produced a significant reduction in UNaV in control rats (from 2.22 +/- 0.46 to 1.14 +/- 0.28 microEq/min, P less than 0.01). By contrast, it induced marked natriuresis in cirrhotic rats (from 0.76 +/- 0.18 to 2.31 +/- 0.70 microEq/min, P less than 0.05). ET significantly increased aldosterone (control rats: 59.3 +/- 2.2 vs. 85.4 +/- 7.4 ng/dl, P less than 0.025; cirrhotic rats: 115.0 +/- 15.8 vs. 163.9 +/- 30.8, ng/dl, P less than 0.05) and ANP (control rats: 20.1 +/- 3.4 vs. 42.7 +/- 7.7, fmol/ml, P less than 0.025; cirrhotic rats: 107.5 +/- 17.3 vs. 214.2 +/- 41.1, fmol/ml, P less than 0.025) and significantly suppressed PRA (control rats: 2.5 +/- 0.5 vs. 0.2 +/- 0.04, ng/ml.hr, P less than 0.025; cirrhotic rats: 16.6 +/- 2.9 vs. 5.0 +/- 1.1, ng/ml.hr, P less than 0.01) in both groups of animals. These results indicate that ET has marked natriuretic properties in cirrhosis with ascites due to inhibition of tubular sodium reabsorption.

Animals↗

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

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↗

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↗