Furosemide dynamics in conscious rabbits: modulation by arginine vasopressin.

The aims of this study were to assess the influence of arginine-vasopressin (AVP) on the pharmacodynamics and kinetics of furosemide. To this purpose, the response and the kinetics of furosemide (5 mg/kg i.v.) were studied in two groups of rabbits, one control and one receiving an infusion of AVP (2.5 ng/kg/min). The infusion of AVP generated mean plasma levels of 35 pg/ml, and in these rabbits osmolal clearance was increased, free water clearance was reduced, and renal plasma flow was reduced by 25% (p < 0.05). High AVP plasma levels increased the natriuresis (p < 0.01) and the urinary excretion of prostaglandin E2 (UPgE2V; p < 0.01). The increase in UPgE2V was associated with AVP plasma concentrations (r = 0.8248; p < 0.001). AVP reduced the increment in natriuresis and diuresis elicited by furosemide from 163 +/- 20 to 87 +/- 20 mumol/min (p < 0.05) and from 1.22 +/- 0.11 to 0.83 +/- 0.13 ml/min (p < 0.05). The infusion of AVP enhanced furosemide metabolic clearance but diminished its renal clearance, resulting in a decrease in the rate of furosemide urinary secretion. It was concluded that high plasma levels of AVP reduce furosemide natriuresis, presumably because of a decrease in furosemide urinary secretion.

Water and sodium homeostasis in conscious rabbits: role of arginine-vasopressin.

The aim of this study was to assess the role of arginine-vasopressin (AVP) on extracellular water distribution (VE) and on the urinary excretion of sodium in conscious rabbits with or without water deprivation. The study included two groups of animals. The first group involved two subgroups, both receiving an infusion of 0.9% NaCl-5% glucose (50-50, v:v) at the rate of 24 ml/hr to adequately hydrate the rabbits, but one received 2.5 ng/min/kg of AVP with the infusion; 120 min later, a bolus of inulin was injected to assess the distribution in the extracellular water. The rabbits of the second group were divided into 3 subgroups, receiving a 0.9% NaCl-5% glucose (50-50, v:v) infusion, at the rate of 6 ml/min; two subgroups received AVP, at the rate of 2.5 or 5 ng/min/kg; 40 minutes later, all animals received a bolus of inulin. In adequately hydrated rabbits, the infusion of AVP generated plasma levels of 35 +/- 7 pg/ml; the VE decreased from 204 +/- 23 to 111 +/- 10 ml/kg (p < 0.01) because of a decrease in plasma (VP) and interstitial volumes (VI). In the same group, natriuresis and osmolal clearance increased and free water clearance decreased. In rabbits deficiently hydrated, AVP reached plasma levels of 47 +/- 18 and 86 +/- 12 pg/ml following the 2.5 and 5 ng/min/kg infusions, respectively. In these animals, high plasma levels of AVP did not diminish VE but decreased the diuresis and osmolal clearance. It is concluded that in adequately hydrated rabbits, pathophysiological plasma levels of AVP shift the water from the VE to the intracellular space and increase the natriuresis, but in partially hydrated rabbits, the infusion of AVP maintains plasma volume constant because of an antidiuretic effect.

Furosemide dynamics: influence of dietary sodium and of saralasin.

The influence of dietary sodium and saralasin on the natriuretic and diuretic response to furosemide (5 mg/kg i.v.) was studied in three groups of conscious rabbits maintained for 4 weeks on either a normal sodium diet (NSD), or a low sodium diet (LSD) or a high sodium diet (HSD). Neither the sodium content in the diet nor saralasin affected glomerular filtration rate or renal plasma flow. Compared to the NSD, an LSD did not affect the furosemide-induced increment in urinary excretion of sodium (dUNaV) but increased the increment in urinary excretion (dUV) (p less than 0.05). An HSD reduced the furosemide-induced dUNaV and dUV (p less than 0.05). Plasma renin activity (PRA) increased following furosemide administration in animals on an NSD and an LSD, but not in those on an HSD. Independent of diet, a positive correlation occurred between the increment in PRA and the dUNaV (p less than 0.001). Saralasin increased PRA and decreased baseline urinary excretion of sodium (UNaV). In addition, in rabbits on an LSD, saralasin reduced the furosemide-induced dUNaV and dUV by 34 and 27% (p less than 0.05), respectively. It is concluded that furosemide-induced diuresis is increased in rabbits on an LSD and decreased in rabbits on an HSD. In animals on an LSD, the increase in furosemide response appears to be associated with changes in the activity of the renin-angiotensin system and in rabbits on an HSD, the decrease in furosemide effect is probably the net result of several factors.

Effect of moderate hypoxemia on atrial natriuretic factor and arginine vasopressin in normal man.

The object of this study was to assess the effect of moderate acute hypoxemia on plasma concentrations of atrial natriuretic factor (ANF), arginine vasopressin (AVP), plasma renin activity (PRA) and urinary excretion of prostaglandin E2 (UPGE2V). Eight volunteers were exposed for 2 hours to a gas mixture containing 10% O2, 4.5% CO2 and 85.5% N2. Hypoxia increased diastolic blood pressure and free water clearance. Hypoxia did not change the AVP, PRA or UPG2V, although increased ANF from 17.7 +/- 3.4 pg/mL to 27.2 +/- 1.7 pg/mL (p less than 0.005) at 120 minutes. ANF changes were closely associated with the rise in blood pressure.

Furosemide pharmacodynamics: effect of respiratory and acid-base disturbances.

The aims of this study were to investigate the effect of changes in arterial blood gases and pH on furosemide pharmacodynamics and kinetics. Five groups of conscious rabbits were used: a control group breathing air with normoxia and normocarbia; a second group with hypercapnia and respiratory acidosis; a third with hypoxemia; a fourth with hypercapnia and respiratory acidosis combined with hypoxemia (HCHO); and the fifth group with metabolic acidosis. All experimental conditions, except hypoxemia, increased sodium tubular reabsorption and therefore, decreased urinary excretion of sodium. Renal blood flow was decreased by HCHO and metabolic acidosis. In response to 5 mg/kv i.v. of furosemide, natriuresis and diuresis were decreased by an average of 44% in animals with HCHO (P less than .05). The kinetics of furosemide were not affected by any of the experimental conditions except HCHO, in which the renal clearance of furosemide was reduced from 7.5 +/- 1.4 ml/min/kg (controls) to 2.7 +/- 0.7 ml/min/kg (P less than .05). The reduction in renal clearance of furosemide was associated with a decrease in urinary excretion of sodium (P less than .05). The reduction in renal clearance of furosemide was probably secondary to the decrease in renal blood flow and an increase in furosemide tubular reabsorption. Finally, HCHO did not decrease plasma volume, suggesting that the reduction in renal blood flow was secondary to blood flow distribution. In conclusion, only hypercapnia and respiratory acidosis combined with hypoxemia decreases the natriuretic and diuretic effect of furosemide.