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...

Changes in urinary volume and electrolyte excretion were monitored after the injection of cholinergic and monoaminergic drugs into the third cerebral ventricle of conscious male rats made diuretic by an intravenous infusion of 5% dextrose. A natriuretic and kaliuretic response was induced by the intraventricular injection of norephrine (NE) or carbachol, whereas dopamine (DA) had no effect. The beta-receptor stimulator isoproterenol (ISO) induced an antinatriuretic and antikaliuretic effect. Intraventricular injection of the alpha-adrenergic blocker phentolamine abolished the natriuretic response to NE and carbachol and to intraventricular hypertonic saline (HS). By contrast, the beta-adrenergic blocker propranolol induced a natriuresis and kaliuresis when injected alone and an additive effect when its injection was followed by NE or HS. Propranolol potentiated the natriuretic response to carbachol. Cholinergic blockade with atropine diminished the response to NE and blocked the natriuretic response to HS. It is suggested that sodium receptors in the ventricular wall can modify renal sodium excretion via a stimulatory pathway involving cholinergic and alpha-adrenergic receptors and can inhibit sodium excretion via a tonically active beta-receptor pathway.

Sinoaortic baroreceptor denervation (SAD) results in increased osmotically induced secretion of vasopressin (VP) and oxytocin (OT) and increased cardiovascular responses to many centrally acting pressor agents. Studies were conducted to determine whether SAD increases the cardiovascular and endocrine responses to direct and peripheral osmotic stimulation of the supraoptic nucleus (SON). SON microdialysis was performed in urethane-anesthetized male rats with measurement of dialysate peptides, mean arterial pressure (MAP) and heart rate. Experiment 1 tested the effect of direct stimulation of the SON with hypertonic NaCl in SAD, sham-operated (control) and intake-matched (matched) rats. Osmotically induced VP release into the SON was significantly greater in SAD than in control or matched groups. VP release peaked at 36 ± 13 and 15 ± 7 pg in SAD and controls, respectively, with no increase observed in the matched group. Plasma VP was significantly elevated after SON osmotic stimulation with no differences observed among the groups. The pressor response to osmotic stimulation was greater in SAD (29 ± 4 mm Hg) than in control (20 ± 3 mm Hg) and matched animals (15 ± 3 mm Hg). Experiment 2 tested the effect of intraperitoneal injection of hypertonic NaCl on SON VP and OT release. SAD rats showed an increased central VP response to peripheral osmotic stimulation, a 64-fold increase in SAD as compared to a 4-fold one in controls. Central OT release was not significantly altered (peak of 22 ± 6 vs. 11 ± 4 pg, SAD vs. control). A direct SON osmotic challenge given 3.5 h after the intraperitoneal test confirmed an increased VP responsiveness in the SAD group. Plasma VP and OT were significantly increased after intraperitoneal hypertonic saline with no difference observed between groups. The MAP response to intraperitoneal hypertonic saline was greater in the SAD group with an elevation of 37 ± 4 versus 18 ± 3 mm Hg observed in SAD versus control subjects. These results demonstrate that baroreceptor denervation produces a state of heightened osmotic sensitivity for VP neurons, with evidence for increased central VP release to both direct and peripheral hypertonic NaCl stimulation.

Sinoaortic baroreceptor denervation is reported to produce exaggerated centrally derived cardiovascular and endocrine responses. We examined the effect of sinoaortic denervation (SAD) on the cardiovascular and endocrine responses to two acute stressors, footshock and immobilization, in male Sprague-Dawley rats. Parameters measured were mean arterial pressure (MAP), heart rate (HR) and plasma levels of oxytocin (OT) and vasopressin (VP). Baseline MAP was elevated in the SAD group (≈25 mm Hg) and footshock stress increased arterial pressure equivalently in both groups. This stress caused tachycardia and increased plasma OT, with a tendency for the SAD group to show blunted responses. Immobilization increased HR but caused no change in MAP and no significant difference between the groups. This form of stress also increased plasma OT, and again the SAD group showed a diminished response. Plasma VP was not significantly altered by either stressor. The results of these studies indicate that SAD does not uniformly increase the cardiovascular and endocrine responses to all stressors or centrally derived stimuli. These results also suggest that the lack of an increase in plasma VP is not related to baroreceptor-mediated inhibition of secretion under stressful conditions.