Renal excretory function in conscious Long Evans and vasopressin deficient (Brattleboro) rats after endothelin-A receptor inhibition.

All experiments were performed on conscious, freely moving male Long Evans as well as Diabetes incipidus (Brattleboro) rats (300-320 g). The endothelin-A (ETA) receptor antagonist BQ-123 (Neosystem) was administered through femoral vein cannula. Arterial blood pressure was measured trough femoral artery catheter. The bladder was cannulated for urine collection via a small suprapubic incision. After a 40 min control period BQ-123 infusion (16.4 nmol/kg/min, 25 microliters/min) was started and continued for 50 min. The effect of 32.8 nmol/kg/min BQ-123 infused in conscious Brattleboro rats was also investigated. Plasma and urine concentrations of sodium, potassium and chloride as well as osmolality were determined. Glomerular filtration rate (GFR) was estimated using the clearance of endogenous creatinine. Endothelin-A receptor inhibition by 16.4 nmol/kg/min BQ-123 infusion in conscious Long-Evans rats decreased urine flow rate by 38.4% (p < 0.02) and increased urine osmolality by 30.3% (p < 0.05). Sodium, potassium, chloride excretion did not alter. Endothelin-A receptor inhibition by 16.4 nmol/kg/min and by 32.8 nmol/kg/min BQ-123 infusion in conscious Brattleboro rats did not produce any change in urine flow rate, urine osmolality or excretion of the electrolytes studied. Endothelins acting via ETA receptors may function as an inhibitor of water reabsorption in the kidneys of conscious rats.

Defective regulation of vasopressin gene expression in Brattleboro rats.

The Brattleboro rat has severe diabetes insipidus due to an autosomal recessive trait resulting in the inability to synthesize detectable amounts of hypothalamic vasopressin. To determine whether this abnormality is due to a regulatory defect in the Brattleboro rat's vasopressin gene, we studied changes in the hypothalamic content of vasopressin mRNA in normal Long-Evans and homozygous Brattleboro rats subjected to osmotic stress and correlated these changes with systemic responses to water deprivation. We report that the Brattleboro rat does have a marked defect in the regulation of vasopressin gene expression consisting of an inability to increase hypothalamic vasopressin mRNA content in response to severe osmotic stress.

Sodium intake as a determinant of urinary prostaglandin excretion. Studies in the Brattleboro rat.

In order to investigate the effects of changes in sodium (Na) balance on the renal production of prostaglandins (PG) E2 and F2 alpha in the absence of antidiuretic hormone (ADH), studies were performed in Brattleboro rats, without endogenous ADH, and in heterozygote Long Evans rats which served as controls. All rats received a diet virtually devoid of Na, with distilled water ad libitum, and Na intake was modified by adding different quantities of Na to the drinking water. Three groups were studied for each strain: normal Na intake, low Na intake and Na loading. At the end of a 14 day diet period, urinary PGE2 and PGF2 alpha were measured by radioimmunoassay in collections obtained for three consecutive days. In the Na depleted animals, both PGE2 and PGF2 alpha decreased. The PGE2/PGF2 alpha ratio (E/F ratio) was unchanged. In contrast, Na loading induced a significant decrease of PGE2 but PGF2 alpha increased, though not significantly. The E/F ratio was significantly decreased. The results were qualitatively similar in the presence or absence of ADH, but the Brattleboro rats, overall, excreted less PGs than controls. The results suggest that changes in Na balance are major factors influencing urinary PG excretion. These substances probably play a role in the modifications of Na handling by the kidney in different balance states.