Search PubMedSearch

Biomedical subjects

A Verniory

Publications and source records attributed to A Verniory.

At least 19 recordsLinked to original sources

Interaction between nonsteroidal anti-inflammatory drugs and loop diuretics: modulation by sodium balance.

Nonsteroidal anti-inflammatory drugs have been shown to decrease the natriuretic response to loop diuretics in many but not all studies. Recently, indomethacin was shown not to affect the natriuretic response to the new loop diuretic torasemide in healthy volunteers. Inasmuch as sodium balance has been reported to modify the effect of indomethacin on furosemide-induced natriuresis in dogs, we investigated the effect of indomethacin, under two sodium balances (50 and 150 mEq/day), on the natriuretic response to two doses of torasemide in six healthy volunteers. Under the low sodium diet, indomethacin reduced the natriuretic response to torasemide like that to furosemide. In contrast, on the normal sodium diet, indomethacin failed to affect the natriuretic response to torasemide. Indomethacin reduced base-line and diuretic-induced increase in plasma renin activity, plasma angiotensin II levels and urinary excretion of prostaglandin 6-keto F1 alpha to a similar extent under the two sodium diets. Our data show that indomethacin reduces the natriuretic response to torasemide in humans. Dietary sodium restriction is a significant determinant of the interaction between nonsteroidal anti-inflammatory drugs and loop diuretics in healthy volunteers, presumably because it allows loop diuretics to provoke an increase in renal blood flow which participates in their natriuretic action and is blocked by nonsteroidal anti-inflammatory drugs.

Adult

Indirect evidence of glomerular/tubular mixed-type postexercise proteinuria in healthy humans.

Hypothetical mechanisms have been postulated to explain the presence of proteins in urine after severe exercise. Recently, it has been shown that several amino acids inhibit tubular protein reabsorption. Seven healthy men, hyperhydrated, were studied during a 2-min bicycle exercise at supramaximal load. The subjects were tested without or with lysine perfusion (0.4 g/kg body wt iv). In both testing conditions, blood lactate increased to 13.8 mmol/l. Total protein urinary excretion increased to 1.10 and 1.67 mg/min, without and with lysine perfusion, compared with 79 micrograms/min at rest. In the meantime, albumin excretion increased 48- and 74-fold, respectively, while beta 2-microglobulin excretion increased 97- and 1,043-fold compared with basal values. The renal clearance of albumin increased to 8.4 microliters/min without lysine and to 12.0 microliters/min with lysine perfusion (rest 0.18). beta 2-Microglobulin clearance increased to 10.0 and 39.3 ml/min, respectively (rest 0.05). These data clearly demonstrate that postexercise proteinuria is of mixed type after exhaustive short-term exertion. Both increased glomerular permeability and partial tubular reabsorption inhibition to proteins appear to be involved.

Adult

Failure of indomethacin to impair the diuretic and natriuretic effects of the loop diuretic torasemide in healthy volunteers.

The effects of torasemide, a new potent loop diuretic, on renin release, water and sodium excretion were investigated in young healthy volunteers before and after 3 days of treatment with indomethacin. Torasemide 20 mg i.v. induced a rapid and biphasic increase both in plasma renin activity and plasma angiotensin II levels, which was almost completely abolished by pretreatment with indomethacin. Torasemide also increased urine volume, sodium excretion and, during the first hour after dosing, the creatinine clearance. None of the latter effects was impaired by indomethacin pretreatment. It is concluded that, like other loop diuretics, torasemide stimulates renin release by increasing renal prostaglandin production. However, at variance with what is observed with other loop diuretics, the diuretic and natriuretic effects of torasemide as well as the change in creatinine clearance do not appear to be inhibited by indomethacin.

Adult

Relationships between blood pressure, heart rate and plasma epinephrine, norepinephrine, angiotensin II concentrations, plasma renin activity during chronic guanfacine therapy in patients with essential arterial hypertension.

The evolution of blood pressure, heart rate, epinephrine, norepinephrine, angiotensin II and plasma renin activity has been studied in 10 patients with essential arterial hypertension before and during a two months period of treatment with guanfacine, a new centrally acting hypotensive drug. Guanfacine was proven effective in lowering both systolic and diastolic supine and standing blood pressure. A decrease in supine and standing norepinephrine plasma concentrations and plasma renin activity was observed. No change was seen in epinephrine or angiotensin II. The fall in supine blood pressure observed during the treatment period was positively correlated with the change in norepinephrine.

Angiotensin II

Relationships between plasma epinephrine, norepinephrine, dopamine and angiotensin II concentrations, renin activity, hemodynamic state and prognosis in acute heart failure.

The relationships between hemodynamic state and plasma components of the renin-angiotensin and adrenergic nervous systems were studied in 42 patients admitted to an intensive care unit with acute heart failure. Patients were allocated to four subsets according to cardiac output and pulmonary wedge pressure. Plasma renin activity and angiotensin II were abnormally high in most patients with cardiac output less than or equal to 3.81 X min-1 and pulmonary wedge pressure greater than or equal to 18 mm Hg in contrast with values of patients of the 3 other subsets, which overlapped the normal range. On the other hand, plasma catecholamines were abnormally high in most patients. Angiotensin II was positively correlated with pulmonary wedge pressure, urea and catecholamines and negatively correlated with cardiac output and natremia. Norepinephrine was uncorrelated with hemodynamic parameters but epinephrine was negatively correlated with cardiac output. A discriminant linear function was calculated for prognosis of survival: cardiac output was the most important factor. The rise of angiotensin II and epinephrine were not unfavorable factors if their correlations with other factors (e.g. cardiac output and urea) were taken into account.

Acute Disease

[Current concept of the mechanism of proteinuria].

Plasma proteins cross the glomerular basement membrane in inverse proportion to their molecular dimension; molecules larger than serum albumin are completely excluded from the glomerular filtrate. This filtration, which is purely passive, also depends of the electrical charge of the proteins; negatively charged proteins are indeed repelled by the negatively charged layer of sialogylcoproteins present along the outer surface of the epithelial cell membrane and extending to the glomerular basement membrane. The filtered proteins are selectively absorbed by the proximal tubular cells and are hydrolyzed by lysosomal enzymes. This results in a renal catabolism of proteins the importance of which depends on their ability to cross the glomerular barrier. In renal disease, proteinuria results either from an increased permeability of the glomerular basement membrane (selective or non-selective glomerular proteinuria) or from a diminished tubular reabsorption of normally filtered proteins of low molecular weight (tubular proteinuria).

Blood Proteins

Effect of sotalol on haemodynamics and renin-angiotensin-aldosterone system in hypertensive patients.

1. Twenty-three hypertensive patients were treated by sotalol, a pure beta-adrenergic receptor blocking agent. The drug produced a significant decrease of blood pressure in nineteen patients. 2. On average, cardiac index decreased but not significantly; heart rate decreased and stroke index increased significantly. Total peripheral resistance varied in both directions. 3. Sotalol determined a fall in plasma renin concentration (only significant in the high-renin group), a fall in plasma angiotensin II concentration and in urinary excretion rate of aldosterone accompanied by a rise in plasma potassium concentration. 4. The fall of blood pressure was not correlated with the decreases of renin and angiotensin II concentrations or excretion rate of aldosterone. However, in the placebo period plasma angiotensin II concentration was significantly correlated with total peripheral resistance; during sotalol treatment the variations of these two parameters seemed also to be correlated. 5. There was a poor correlation between decreases of cardiac output and of blood pressure; it was impossible to foresee the magnitude of the lowering of the blood pressure from the initial cardiac index. 6. The association of a diuretic with sotalol enhanced the hypotensive effect of the beta-receptor blocking drug, without significant increase of plasma renin and angiotensin II concentrations.

Adult

Determination of glomerular intracapillary and transcapillary pressure gradients from sieving data. II. A physiological study in the normal dog.

The two theoretical models proposed previously to calculate the intracapillary and transcapillary glomerular pressure gradients from the sieving of macromolecules such as PVP have been used to analyse in 22 normotensive dogs the sieving curve relating the sieving coefficients, phi, to molecular size (phi: glomerular clearance of PVP fractions/GFR). Neither the "local c2" model-filtrate unmixed at the outer face of the capillaries walls--nor the constant c2 model-filtrate well mixed--allowed to obtain realistic values for the hemodynamical parameters. Indeed with the local c2 model, the best fit between calculated and experimental sieving curves could be obtained only by reversing the intracapillary pressure gradient; conversely the constant c2 model obliged to decrease the intracapillary pressure so abruptly along the capillaries, that retrofiltration took place in the distal parts of the vessels. This difficulty has been overcome by combining the two models; the so-called "hybrid model" considers that the filtrate is well mixed in the vicinity of the urinary pole only. The following results were obtained: 1. PGCa and PGCe (intracapillary pressures at the afferent and efferent extremities of the capillaries) equal to 49.7 +/- 1.03 and 41.8 +/- 1.00 mm Hg respectively. 2. Pressure equilibrium is generally reached at the efferent extremity of the vessels. 3. The slope of PGC (see article) varies inversely to FF. (filtration fraction). 4. The model, however, does not allow to rule out the possibility of retrofiltration.

Animals

Determination of glomerular intracapillary and transcapillary pressure gradients from sieving data. I. A mathematical model.

Determination of glomerular intracapillary and transcapillary pressure gradients from sieving data. A biomathematical model is described to calculate the intracapillary and transcapillary glomerular pressure gradients from the sieving coefficients (phi: fractional clearances/GFR) of macromolecules such as polyvinylpyrrolidone (PVP). Two differential equations have been developed. The first one calculates local values for GFR in terms of local values for PGC (intracapillary hydrostatic pressure) and pi (oncotic pressure). The second equation calculates the clearance of PVP equimolecular fractions, the sieving equations previously described (24) being used to derive the concentrations of PVP in the filtrate (c2). Two variants of the second equation have been considered, assuming the filtrate in contact with the membrane either "well stirred" or "unstirred" (constant c2 and local c2 gradient models respectively). Computer simulations have been used to illustrate how the sieving curve is modified when the five parameters on which depends the shape of the curve are changed one by one. The sieving curve relates phi to a(s) (hydrodynamically equivalent molecular radius). The determining parameters are: GFP, the mean effective glomerular filtration pressure, epsilon, the slope of the intracapillary pressure, FF, the filtration fraction, Cp0, the protein concentration in arterial plasma and r, the pore radius which is the only structural parameter involved when one assumes the glomerular membrane crossed by cylindrical pores of uniform size and length. The shape of the sieving curve is modified significantly enough by changing GFP, FF and r within reasonable limits, to make it possible to derive GFP and r from experimental sieving data for macromolecules such as PVP or dextrans.

Capillaries