动物实验
Rat strains[2]
Male double transgenic rats (dTGR) withhuman angiotensinogen and renin genes (hREN) L10 × (hAOGEN) 1623 were obtained(5–6weeks of age, weighing 161 ± 2.6g with an average mean BP of 159 ± 2.6mmHg). Following acclimatization and a health examination, rats were housed ingroups of three in standard cages with wire mesh tops and standardized softwoodbedding, synchronized to a 12-hourlight–dark cycle, at ambient temperature 23 ±2oC. A standard rat diet and tap water were supplied ad libitum.
Effectof avosentan on diuresis and blood pressure in hypertensive rats
The purpose of this experimental protocolwas to examine the effect of avosentan on diuresis in hypertensive rats. Avosetanwas administered by gavage to dTGR as single doses (six rats per treatmentgroup: 0.1, 1.0, 10 and 100mg/kg and vehicle). Rats were placed after drugadministration in metabolic cages for 24 h to assess fluid electrolytehomeostasis. On this occasion, the following urine parameters were determinedfor each collection period: water intake (ml), diuresis (ml), Na+ concentration(mmol/L), natriuresis/24 h. After 24h from each dosing, blood samples(approximately 0.3 ml/sample) were collected in all animal groups under lightisoflurane anesthesia. The blood samples were collected in Li-heparinized tubesfor hematocrit measurement.
In a parallel study, six rats per treatmentgroup were instrumented for telemetry BP recording. A telemetry transducer wasimplanted under anesthetic conditions (isoflurane anesthesia), its catheterintroduced into the abdominal aorta just below the bifurcation of the renalarteries, and the sensor fixed to the peritoneum.
