pituitrin and 2-bromoethylamine

The induction of selective renal medullary damage by 2-bromoethylamine hydrobromide (BEA) results in polyuria and raised blood pressure. In view of the likely elevation of plasma vasopressin we have investigated the role of vasopressin (AVP) in the elevated blood pressure in this model. Plasma vasopressin levels in BEA pretreated rats were raised significantly (2 +/- 0.6 pg/ml vs 0.8 +/- 0.1 in normal rat, P less than 0.05) but not to pressor levels. In addition, pressor responsiveness was investigated in renal medullary damaged rats. There was a reduced response to vasopressin and noradrenaline but no alteration with angiotensin II. A specific V1, receptor AVP antagonist [d(CH2)5Tyr(Me)AVP] produced no fall in blood pressure but returned the noradrenaline dose-response curve to normal. This suggests an interaction between vasopressin and the sympathetic nervous system in this model. Thus there is no evidence that vasopressin contributes to the rise in blood pressure produced by chemical renal medullectomy and other mechanisms have to be sought.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Blood Pressure; Dose-Response Relationship, Drug; Ethylamines; Female; Hypertension, Renal; Kidney Medulla; Norepinephrine; Rats; Renin; Vasopressins

2-Bromoethylamine hydrobromide (BEA) causes complete papillary necrosis within 24-hr of i.v. administration. The mechanism of this effect is unknown. To characterize further the effect of BEA in transporting epithelia, the urinary bladders of toads and turtles were exposed to varying concentrations of BEA in vitro. In the toad bladder, both cyclic AMP- and vasopressin-stimulated water flow were significantly inhibited after 3 hr of exposure to BEA at a concentration as low as 2.5 X 10(-4) g/ml; after 1 and 2 hr no effect on water transport was observed. Serosal administration of BEA to both toad and turtle bladders significantly inhibited sodium transport to 54% of control at the end of 3 hr. The effect on sodium transport was seen as early as 10 min. The threshold for the effect on sodium transport occurred at a concentration less than that observed for water transport. By contrast, BEA had no effect on hydrogen ion secretion in the isolated turtle bladder over a wide range of concentrations. In fact, after 1 hr, BEA significantly stimulated hydrogen ion secretion. In homogenates of stripped turtle bladder mucosa, BEA significantly inhibited total Na-K adenosine triphosphatase and ouabain sensitive Na-K adenosine triphosphatase. Thus, in anuran membranes, BEA inhibits water and sodium transport but has no effect on acidification. These results suggest that its action in vivo may be related to alterations in cell volume regulation resulting from inhibition of sodium transport rather than a nonspecific toxic effect on the inner medullary epithelium.

Topics: Animals; Body Water; Bufo marinus; Cyclic AMP; Ethylamines; Hydrogen; Kidney Medulla; Necrosis; Sodium; Sodium-Potassium-Exchanging ATPase; Urinary Bladder; Vasopressins

We studied the pathogenesis of chemically induced papillary necrosis in six groups of rats. Papillary necrosis was produced by a single injection of 2-bromoethylamine hydrobromide (BEA), 50 mg, i.v.; the animals were followed for 7 to 10 days after the administration of the compound. Following BEA, heterozygous Brattleboro rats developed all the functional and morphologic lesions of papillary necrosis that we previously described in Sprague-Dawley rats. They were unable to maintain sodium balance when dietary sodium was withdrawn. Homozygous Brattleboro rats, on the other hand, developed none of the manifestations of papillary necrosis (that is, animals with central diabetes insipidus were protected completely from the nephrotoxic effects of BEA). They adapted normally to a zero sodium diet. Chronic administration of vasopressin to homozygous Brattleboro rats fully restored the toxic effects of BEA. Lowering urinary concentrating ability by inducing a water diuresis in Sprague-Dawley rats completely protected against BEA-induced papillary necrosis. Decreasing papillary solute concentration by furosemide or increasing urine flow after abrupt withdrawal of vasopressin to homozygous Brattleboro rats did not protect against BEA-induced papillary necrosis. We conclude that the combination, but not either alone, of increased urine flow and decreased papillary solute concentration protects against the development of BEA-induced papillary necrosis.

Topics: Animals; Diuresis; Ethylamines; Heterozygote; Homozygote; Kidney Concentrating Ability; Kidney Papillary Necrosis; Male; Rats; Rats, Brattleboro; Rats, Inbred Strains; Vasopressins