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The microinjection of hypertonic sodium chloride solution into the third ventricle elicits natriuresis, kaliuresis, and a decline in urine volume in several species (1)(2)(3)(4). Natriuresis also follows the intraventricular injection of carbachol ( 5 ) or norepinephrine (4), suggesting that adrenergic and cholinergic synapses may participate in the pathway concerned with the elicitation of central natriuresis and kaliuresis. The mechanism by which these agents induce increased excretion of monovalent cations has not been resolved. To determine if pituitary or hypothalamic hormones might play a role in mediating these responses, lesions were placed in the median eminence of the tuber cinereum of rats and the effects of the lesions on the response to third-ventricular injection of hypertonic saline and norepinephrine were studied.Materials and methods. Male Holtzman rats (250-350 g) were housed communally under conditions of controlled temperature and lighting, and were given free access to tap water and laboratory chow. Using ether anesthesia, bilateral electrolytic lesions were placed in the median eminence region using cathodal current (3 mA) passed for 17 sec as previously described (6). Sham lesions were placed by inserting the electrodes bilaterally to a depth of 5 mm beneath the calvarium without passage of current. After at least 5 days the animals were anesthetized with ether and subjected to the second series of procedures (cannulation of the third ventricule, jugular vein, and urinary bladder) as previously described (4). They were used for the experiments 1-2 days later. Daily water intake was measured in shamoperated rats and those with median eminence lesions.For the experimental procedure, the animals were placed in individual metabolic cages and an infusion into the external jugular vein of 5% dextrose (0.19 ml/min) was begun. Urine samples were collected at 15min intervals and when the rate of urine flow had reached a plateau, 2 pl of 2 M NaCl or 5 pg of norepinephrine bitartrate in 2 pl of 0.9% NaCl were injected into the third ventricle. This was followed by the collection of an additional six urine samples. Urine volume and Na+ and K+ were measured in each sample. The site and extent of the lesion was determined by microscopic examination of frozen frontal hypothalamic sections cut at 15-pm and stained with thionin.Significance of differences between means of two groups was determined by Student's t test.Results. Effect of median eminence lesions on the response to hypertonic saline. An increase in the sodium concentration of the cerebrospinal fluid (CSF) elicits a natriuretic effect in the conscious animal (4). This effect was still observed when hypertonic saline (2 pl of 2 M NaCl) was injected into the third ventricle in the animals with sham lesions (Fig. 1); however, destruction of the median eminence region prevented this natriuresis. Likewise, there was no increase in potassium excretion following the intraventricular injection of hypertonic saline into the rats with electrolytic lesions...