A Novel Computer-Driven, Servo-Controlled Fluid Replacement Technique and Its Application to Renal Function Studies in Conscious Rats

Abstract

1. A new rat model has been developed allowing body fluid status to be accurately controlled and maintained throughout experimentation by computer-driven, servo-controlled replacement of spontaneous urinary fluid losses. 2. Experiments in vitro were performed to test the accuracy of the servo system, and experiments in vivo were carried out to re-assess basic renal function in servo-controlled vasopressin-replete Long Evans and vasopressin-deficient Brattleboro rats. The model was further evaluated in water-diuretic Wistar rats with or without administration of a vasopressin V2-receptor agonist, 1-desamino-8-D-arginine vasopressin. 3. The data gained from the present study indicate the suitability of the servo-controlled replacement system for conscious renal function studies in three different rat strains. Haemodynamic and renal function variables measured were demonstrated to be stable throughout a 5 h experimental procedure and reproducible between repeated experimental occasions over a 14 day post-operative period. 4. Using the servo-control technique, the expected action of 1-desamino-8-D-arginine vasopressin on renal water handling was demonstrated, but the natriuretic effect reported by some workers was not evident. 5. Since the servo-controlled fluid replacement technique maintains many of the inherent differences between vasopressin-replete Long Evans and vasopressin-deficient Brattleboro rats and eliminates the changes in body fluid volume during transition from a diuretic to an antidiuretic state, the model confers an advantage over previously employed constant infusion protocols.

The Effect of Chloroquine on Renal Function and Vasopressin Secretion: A Nitric Oxide-Dependent Effect

“…This system relies on urine flow information from a balance being transmitted to an adjustable pump via a computer. A program developed at the University of Manchester (Burgess et al, 1993) allows the computer to detect changes in urine output gravimetrically and make changes to the infusion rate of the pump accordingly, to precisely replace intravenously the volume of fluid lost as urine.…”

Differential Down-Regulation of Aquaporin-2 in Rat Kidney Zones by Peripheral Nociceptin/Orphanin FQ Receptor Agonism and Vasopressin Type-2 Receptor Antagonism

“…Intravenous infusion of ZP120 (1 nmol/kg/min) or OPC31260 (32 nmol/kg/min) then was started, and urine was sampled in consecutive 30-min periods during the next 4 h. Total body water content was kept constant during ZP120 or OPC31260 treatment by servo-controlled i.v. replacement of urine losses with 50 mM glucose (Burgess et al, 1993;Hadrup et al, 2004). The mean arterial pressure was measured throughout the study, and arterial blood samples (0.3 ml) were drawn every hour.…”

“…First, we conducted renal clearance experiments in chronically catheterized rats in a setup where renal water losses were replaced by servo-controlled infusion of 50 mM glucose to avoid physiological antagonism (Burgess et al, 1993). In this model, ZP120 and the V 2 -receptor antagonist OPC31260 were infused i.v.…”

Renal Action of Acute Chloroquine and Paracetamol Administration in the Anesthetized, Fluid-Balanced Rat

“…Briefly, urine flow rate, determined gravimetrically, is transmitted to an adjustable pump via a computer. A program developed at the University of Manchester (Burgess et al, 1993) allows the infusion rate of the pump to be automatically adjusted to precisely replace intravenously the volume of fluid lost as urine. 3 H]inulin (6 Ci) was injected via the venous cannula and servo-infusion replacement initiated.…”