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Brattleboro rats were housed singly in metabolic cages and continuously infused with saline. Timed urine collections were analyzed for Na+ and K+; oxytocin (OT)-like material was estimated by RIA. OT infusions reduced urine flow and increased Na+ output. Urinary Na+/K+ ratios rose during OT infusion, falling below control values after infusion. Passive immunization with an OT antiserum reduced but did not prevent these renal effects of OT. In a second experiment, immunization had no effect on daily urine volume or Na+ output, even though high titers were achieved and excretion of endogenous OT-like material was reduced. We conclude that endogenous OT has little effect on Na+ excretion in these rats, although pharmacological doses of OT produced their known natriuretic effect.

The hemodynamic effects of 0.6% saline, consumed either from youth (4th week of age) or from adulthood (12th week of age), were studied in unanesthetized, unoperated, and uninephrectomized homozygous female Brattleboro rats. Long-term saline drinking induced a general decrease of blood pressure in unoperated rats which was more pronounced in rats drinking it from youth. The relation of low systemic resistance and high cardiac output (observed at the age of 10-15 weeks) to the high mortality of these rats was discussed. Two phases were recognized in the development of salt hypertension in uninephrectomized rats drinking saline from youth. The increased systemic resistance played a major role during the early phase (13-15 weeks), while changes of body fluids as well as altered arterial compliance contributed to the elevation of systolic blood pressure in the late phase of salt hypertension (20-30 weeks of age). In uninephrectomized rats drinking saline from adulthood, the late blood pressure response was only slightly attenuated in comparison with uninephrectomized rats drinking saline from youth. The absence of increased arterial rigidity in the former group was the only major hemodynamic difference between these two groups of uninephrectomized rats aged 20-30 weeks.

The total restoration of urinary concentrating ability of the DI rat given daily injections of vasopressin takes several weeks, although complete osmotic equilibrium across the collecting duct is manifest within hours. This suggests that there may be other deficiencies of the renal concentrating mechanism that, if corrected by vasopressin treatment, are corrected more slowly. I have focussed on just three possibilities. First, the morphology of the medullary interstitium is different from normal rats. Perhaps associated with this finding are alterations in the levels of medullary glycosaminoglycans which may have a role to play in water balance. Functional and morphological changes in the juxtamedullary nephrons are also evident. Second, the possibility exists that the countercurrent multiplier of the DI rat operates less efficiently than in the normal animal. Finally, reduced synthesis of PGs in the renal medulla of DI rats may also influence the concentrating mechanism, although in a favorable direction. While most (if not all) of these differences are secondary to the lack of vasopressin, in some instances it appears that it is the high water turnover (possibly the altered chemical composition of the medullary interstitium) that is the primary culprit. While the DI rat remains an excellent model for the study of water balance and the action of vasopressin, the presence of multiple defects within the system should be borne in mind. This is particularly true when comparing data obtained following acute treatment with vasopressin versus that following chronic treatment.

We studied the replacement therapy of different doses of AVP in DI rats. It is surprising that relatively high levels of plasma AVP were needed to achieve significant antidiuretic effects. Measured plasma AVP concentrations are less than those predicted from the release rates of AVP by the minipumps. This difference may be due to the subcutaneous mode of release of AVP. The study also provides evidence that urinary excretion of AVP is a good indicator of the plasma AVP level.