Biomedical subjects

M Asbert

Publications and source records attributed to M Asbert.

10 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

Mineralocorticoid escape in patients with compensated cirrhosis and portal hypertension.

Failure to escape from mineralocorticoids in compensated cirrhosis is considered a major argument supporting the overflow theory of ascites. To assess the frequency and mechanism of mineralocorticoid escape in cirrhosis, 9-alpha-fluorohydrocortisone (0.6 mg/day) was administered to 19 patients with compensated cirrhosis, portal hypertension, and no history of ascites who were able to maintain sodium balance on a 250 mmol Na+ diet. Fifteen patients (78.9%) escaped from mineralocorticoids, while 4 patients (21.1%) did not escape and developed ascites. Patients who did not escape had significantly higher cardiac index (4.97 +/- 0.42 vs 3.46 +/- 0.21 L.min-1.m-2) and lower peripheral vascular resistance (485.9 +/- 37.5 vs. 665.8 +/- 32.9 dyne.s.cm-5/m2) than those who escaped. Hepatic venous pressure gradient was not significantly different. The escape phenomenon was associated with a significant increase in mean arterial pressure, creatinine clearance, and atrial natriuretic factor and suppression of plasma renin activity. All of these parameters showed minimal or no changes in patients who did not escape. These results indicate that failure to escape from mineralocorticoids is uncommon in patients with compensated cirrhosis, is related to an inadequate expansion of effective plasma volume due to the accumulation of ascites, and occurs in patients with marked peripheral arteriolar vasodilation.

Adult↗

PubMed1992

Assessment of the renin-angiotensin system in cirrhotic patients. Comparison between plasma renin activity and direct measurement of immunoreactive renin.

The renin-angiotensin system plays an important physiological role and has prognostic significance in cirrhotics with ascites. The degree of stimulation of this system is usually estimated by measuring plasma renin activity after incubation periods of 2-3 h. Recent investigations showed that the direct measurement of immunoreactive renin also estimates the degree of activity of the system. In this study, immunoreactive renin and plasma renin activity (measured at incubation periods of 10, 20, 50 and 180 min) were determined in ten healthy subjects, five hyperreninemic non-hepatic patients and 47 cirrhotics with ascites. Cirrhotic patients showed significantly higher plasma renin activity (5.1 +/- 0.9 ng/ml per h, p less than 0.05) and immunoreactive renin (145.4 +/- 24.4 pg/ml, p less than 0.01) than healthy subjects (1.2 +/- 0.15 ng/ml per h and 25.1 +/- 1.1 pg/ml, respectively). The angiotensin I generation rate was constant during the 3-h incubation in 22 cirrhotics and a close relationship (r = 0.956, p less than 0.001) between plasma renin activity (3.5 +/- 1.6 ng/ml per h) and immunoreactive renin (71 +/- 25 pg/ml) was observed in these patients. In the remaining 25 cirrhotics the generation rate of angiotensin I declined with time and the calculated plasma renin activity at 180 min was lower than the activity calculated at 10 min by 50.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1991

Effect of V1-vasopressin receptor blockade on arterial pressure in conscious rats with cirrhosis and ascites.

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.

Angiotensin II↗

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

Effects of endothelin on renal haemodynamics and segmental sodium handling in conscious rats.

The effects of endothelin (100 and 600 pmol/kg) on renal plasma flow (RPF), glomerular filtration rate (GFR), sodium excretion (UNa V) and segmental sodium handling were investigated in conscious rats. Low-dose endothelin decreased renal plasma flow by 26% without affecting glomerular filtration rate and sodium excretion. High-dose endothelin reduced renal plasma flow, glomerular filtration rate, sodium excretion and lithium clearance by 57, 45, 38 and 52%, respectively. The fall in sodium excretion was not due to a direct effect of endothelin on tubular sodium transport since sodium excretion corrected by glomerular filtration rate and fractional proximal and distal sodium reabsorption did not change throughout the study. These results indicate that the impairment in renal perfusion is responsible for the antinatriuretic effect of endothelin in conscious rats.

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

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

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

Blockade of the hydroosmotic effect of vasopressin normalizes water excretion in cirrhotic rats.

Water retention in cirrhosis has classically been considered to be due to a low distal fluid delivery secondary to increased proximal sodium reabsorption. However, recent studies showing high plasma vasopressin levels in patients and rats with cirrhosis, ascites, and dilutional hyponatremia suggest that a nonosmotic vasopressin hypersecretion could be an alternative mechanism. To investigate the role of vasopressin in water retention in cirrhosis, the renal ability to excrete a water load (50 ml/kg body wt), as estimated by the minimum urinary osmolality and the percentage of the water load excreted during 3 h, was assessed in 10 control rats and in 20 cirrhotic rats with ascites and impaired water excretion and high urinary excretion of vasopressin. Twenty-four hours later, the same procedure was repeated in cirrhotic rats 20 min after the subcutaneous injection (30 micrograms/kg body wt) of d(CH2)5Tyr(Et) VAVP, an antagonist of the hydroosmotic effects of vasopressin (10 rats), or the vehicle (10 rats). Treatment with the vasopressin antagonist normalized water excretion in 9 of the 10 rats. No significant changes in renal water metabolism were observed in the group of rats given the vehicle. These results indicate that vasopressin hypersecretion is the predominant mechanism of the impairment in water excretion in rats with experimental cirrhosis and ascites.

Animals↗