Observations on water and electrolyte metabolism after hypophysectomy or adrenalectomy, in male and female rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain) are confirmed and extended. The diabetic (homozygous, DI) state relative to the non-diabetic (heterozygous, non-DI) state was characterized by (1) water intake of 55-120% body weight; (2) copious urine hypo-osmotic to plasma; (3) greater excretory rates of total solute, Na, Ca and Mg; (4) similar plasma composition except that in male DI rats, K concentration was less, and in female DI rats osmolarity was higher; (5) glomerular filtration rates (GFR) were similar with close correlations between: food and water intakes, water intake and output, urinary Na and K, Na and Cl, K and Cl, and Ca and Mg; (6) both female DI and non-DI rats had lower urinary Na:K ratios and lower plasma Na concentrations than males; (7) female DI rats excreted relatively larger amounts of K and Cl, and had higher plasma Ca concentrations than other groups. Hypophysectomized DI rats had decreased water intake and urine output, decreased solute excretion, decreased loss of osmotically free water, lower excretory rates of Na, K and Cl, and increased urinary osmolarity and K concentrations. Hypophysectomized non-DI rats had increased urinary excretory rates, decreased solute excretion (by 60-70%), decreased osmotically free water absorption, decreased urinary osmolarity, Na and K concentrations, and increased excretory rates of Ca and Mg. Hypophysectomized DI and non-DI rats had increased plasma osmolarity and Na concentration. Plasma renin activities (PRA) were higher in DI than in non-DI rats with female values lower than those of males; values for both sexes of DI and non-DI rats were reduced after hypophysectomy. Adrenalectomized DI rats had about a 50% reduction in water intake, urine output and free water clearance, increased urinary concentration of electrolytes and total solute by day 4 after operation; their Na balance (dietary:urine) did not change significantly in contrast to adrenalectomized non-DI rats in which a greater percentage of dietary Na appeared in the urine. GFR was similarly reduced in adrenalectomized DI and non-DI rats. Plasma osmolarity increased in adrenalectomized male DI, decreased in female DI and non-DI, and did not change in male non-DI rats. Plasma K concentrations increased after adrenalectomy in all groups, only non-DI rats had a significantly decreased plasma Na concentration. There was no sex difference in pituitary oxytocic activity but it was consistently reduced in DI rats; there was little change after adrenalectomy in male DI and non-DI rats; but there was an increase in DI and non-DI females. Pituitaries of DI rats had no measurable ADH activity (except the inherent activity of oxytocin). Pituitary ADH values for male and female non-DI rats were similar and were unaffected by adrenalectomy.

The caudal portion of the spinal cord of elasmobranch fish incorporates a diffuse neuroendocrine system. Using an antiserum raised against urotensin II from a teleost fish (goby) to facilitate purification, a peptide structurally related to urotensin II was isolated in pure form from an extract of neuroendocrine tissue from the spinal cord of the European common dogfish, Scyliorhinus canicula. The primary structure of the peptide was established as: Asn-Asn-Phe-Ser-Asp-Cys-Phe-Trp-Lys-Tyr-Cys-Val. The amino acid sequence was confirmed by chemical synthesis. A comparison of this sequence with those of the known teleost urotensin II peptides shows that the cyclic region of the molecule has been fully conserved between species and suggests that the presence of an acidic residue at position 5 and a hydrophobic residue at position 12 are important features for the biological activity of the peptide. The dogfish spinal cord extract also contained a high concentration of the calcium-binding protein, parvalbumin and the amino acid sequence at its NH2 terminus [residues (1–50)] was determined.

Indices of carbohydrate and lipid metabolism were investigated in male New Zealand genetically hypertensive and normotensive rats. Cross-breeding of male rats of these strains with female Brattleboro diabetes insipidus rats also provided the opportunity to examine the metabolic impact of vasopressin and its deficiency in hypertensive and normotensive rats. Hypertensive and normotensive rats, with or without diabetes insipidus, were fasted for 24 h, exsanguinated and their blood/plasma analysed for various indices of carbohydrate and lipid metabolism. Whilst each group of rats maintained fasted normoglycemia, hypertensive rats, with or without vasopressin-deficiency, were hypoinsulinaemic relative to normotensive counterparts. Moreover, hypertensive or normotensive vasopressin-deficient rats were hypoinsulinaemic relative to vasopressin-replete counterparts. In vasopressin-replete rats, the apparently improved insulin sensitivity in hypertension was associated with significant falls in plasma glucagon, triglycerides and total cholesterol. Finally, normotensive vasopressin-deficient rats were hypoglucagonaemic relative to the vasopressin-replete group. These data demonstrate that independent of vasopressin status, hypertension in the New Zealand strain and the diabetes insipidus hybrid was associated with improved insulin sensitivity. However, endogenous vasopressin exercises an influential role in carbohydrate and lipid metabolism in normotensive rats.