Role Of Vasopressin Research Articles

Role of vasopressin in sympathetic response to paraventricular nucleus stimulation in anesthetized rats.

Vasopressin may play an extrahypothalamic role in the central control of the cardiovascular system, specifically acting as a spinal neurotransmitter in the pathway where the paraventricular nucleus (PVN) alters sympathetic outflow. In this study, the effect of stimulating neuronal cell bodies in the PVN on renal sympathetic nerve activity (RSNA) and the possible involvement of vasopressin in the pathway was investigated in anesthetized rats. The PVN was stimulated by microinjection with 0.2 M D,L-homocysteic acid via a glass micropipette, and the hemodynamic and sympathetic responses were recorded. A computerized sympathetic peak-detection algorithm was applied to recordings of sympathetic discharges to retrieve information about the characteristics of RSNA during PVN stimulation. The algorithm scanned the series of RSNA voltages for significant increases followed by significant decreases in a small cluster of voltage values. Once each synchronized RSNA peak had been detected, its corresponding amplitude and peak-to-peak interval were calculated. PVN stimulation consistently increased the amplitude of RSNA (mean 30 +/- 5.6% over control), arterial pressure, and the peak-to-peak interval of discharges. A V1 vasopressin antagonist intrathecally administered as a 500-pmol dose was subsequently able to completely block the hemodynamic response (blood pressure increase of 14 +/- 5%) and a 35 +/- 6% increase in RSNA in response to PVN stimulation and intrathecal vasopressin. Thus spinal vasopressin is likely to be a neurotransmitter involved in the cardiovascular regulation involving the PVN.

Vasupressin and the Endocrine Response To Stress

This paper highlights the role of vasopressin in the endocrine response to stress at various levels of regulation in the hypothalamic-pituitary-adrenocortical system. Novel data arc presented regarding the interaction of vasopressin and corticotropin-releasing factor (CRF) in rat anterior pituitary cells. In this system CRF-induced cyclic AMP synthesis is under feedback inhibition by intracellular free calcium. Vasopressin enhances the cyclic AMP response to CRF apparently by reducing the efficiency of calcium inhibition. As corticosteroid mediated inhibition of ACTH release is also mediated by a calcium-dependent process, these findings show a mechanism whereby vasopressin may change the set-point of glucocorticoid negative feedback at the pituitary level.

Role of vasopressin and atrial natriuretic factor in response to head-out water immersion

Role of vasopressin and atrial natriuretic factor in response to head-out water immersion

Mechanisms for the diuresis of acute cold exposure: role for vasopressin?

The hypothesis that inhibition of vasopressin (VP) secretion initiates cold-induced diuresis was tested in six Brattleboro homozygous (diabetes insipidus, DI) rats exposed to 60 min at 5 degrees C. For 9-14 days before cold exposure (CE) the rats were treated with VP (750 pg.kg-1.min-1) subcutaneously via osmotic minipumps. Eight vehicle-treated Long-Evans (LE) rats characterized the response to acute exposure at 5 degrees C. Additional groups of six to eight LE and six DI rats were infused with VP (30-90 pg.kg-1.min-1 iv) on the day of CE. The DI rats receiving chronic VP replacement and untreated LE rats exhibited cold-induced diuresis, with peak increases in urine flow (V) of 63 +/- 12 (DIs) and 29 +/- 4 (LEs) microliters.min-1 x 100 g body wt-1. LE rats acutely infused with VP exhibited a diuresis at the two lower doses (peak V was 18 +/- 3 at the 30 and 18 +/- 4 microliters.min-1 x 100 g body wt-1 at the 60 pg.kg-1.min-1 dose), but the diuretic response was completely blunted at the uppermost dose of VP. Cold-induced diuresis was absent at the lowest VP dose in the acutely infused DI rats. A pressor response (30-36 mmHg) to CE was noted with all treatment groups, including those that did not exhibit a diuresis. No changes in glomerular filtration rate (GFR) with CE were observed. These data suggest that when plasma VP levels are controlled by prolonged infusion of VP in the DI rats, other mechanisms can operate to initiate cold-induced diuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of Vasopressin and .ALPHA.1-Adrenergic Mechanism in the Cardiovascular Effects of Intracerebroventricular Administration of Somatostatin in Rats.

To clarify the mechanisms of the cardiovascular responses to Intracerebroventricular administration (i.c.v.) of somatostatin=14 (SS-14), the effects of pretreatment by i.c.v. α-antagonists or intravenous administration (i.v.) of vasopressin antagonist were investigated in conscious male Wistar rats. Plasma arginine vasopressin (AVP) concentration was also measured. The i.c.v. SS-14 (1.0nmol/kg) caused an increase in mean arterial pressure (MAP) of 16±2mmHg and a decrease in heart rate (HR) of -20 ±3 beats/min, and an increase in plasma AVP concentration from 3.2±0.7 to 21.7±2.9pg/ml (p< 0.05). Pretreatment with either i.c.v. phentolamine (200μg/kg) or i.c.v. bunazosin (50μg/kg) significantly attenuated the pressor response (16±2 to 7±2mmHg, p<0.05, or 16±2 to 7±1mmHg, p<0.05, respectively) and the plasma AVP response (21.7±2.9 to 4.8±1.8pg/ml, p<0.05, or 21.7 ±2.9 to 5.2±2.0pg/ml, p<0.05, respectively) to i.c.v. SS-14. Pretreatment with i.c.v. yohimbine (20 μg/kg) did not affect the cardiovascular responses to i.c.v. SS-14. Pretreatment with i.v. AVP antagonist significantly attenuated the pressor response to i.c.v. SS-14 (16±2 to 6±1mmHg, p<0.05). These results suggest that the pressor response to i.c.v. SS-14 is mediated through activation of central α1-adrenergic mechanisms which cause elevation of plasma AVP concentration.(Hypertens Res 1993; 16: 91-96)

Vasopressin administration via microdialysis into the septum interferes with the acquisition of spatial memory in rats

The role of vasopressin (AVP) in the septohippocampal system in spatial memory was studied in 27 male hooded rats of the Long Evans strain. The rats were implanted with a septal microdialysis probe and assigned to 3 groups. Two days later, they were trained on 3 consecutive days (12 daily trials) to locate the hidden underwater platform in the Morris water maze (MWM) while the probes were perfused with either artificial cerebrospinal fluid (aCSF) or aCSF containing vasopressin or the V 1 antagonist d(CH 2) 5Tyr(Me)AVP (AAVP). Another group of rats ( n = 8) remained untreated. Groups receiving microdialysis of aCSF or AAVP acquired the MWM task at the same rate as untreated animals. On the other hand, place navigation learning was significantly impaired by microdialysis of AVP during all sessions. The results indicate that endogenous AVP (at least that affecting the V 1 receptor subtype) is not indispensable for the acquisition of spatial memories in the MWM, whereas excessive presence of synthetic AVP interferes with spatial learning.

Role of vasopressin in aggressive and dominant/subordinate behaviors.

Role of vasopressin in aggressive and dominant/subordinate behaviors.

Vasopressin deficiency abolishes a sexually dimorphic behavior in Brattleboro rats

The role of vasopressin (VP) in a sexually dimorphic behavior, the extinction of a conditioned taste aversion, was investigated in male and female rats of three different genotypes. This behavior was examined with a two bottle test in the wild-type Long-Evans (LE) rats, and then in partially VP deficient heterozygous (HET-BB) and completely VP deficient homozygous (HO-BB) Brattleboro rats. In Experiment 1, non-deprived male and female LE rats were given aversions to a sucrose solution by pairing it with a LiCl injection. The rate of extinction of the aversion upon reexposure to ad lib sucrose solution was examined and observed to be sexually dimorphic. Female LE rats extinguished at a significantly more rapid rate than males. Experiment 2 compared HET-BB and HO-BB male and female rats using the same paradigm. Neither of these VP-deficient groups showed sexual dimorphism of the extinction behavior. The data suggest that intact VP levels are necessary to observe the expression of this sexually dimorphic behavior.

Plasma vasopressin and cortical nephron function in aging rats

The role of vasopressin and Henle's loop transport in age-related polyuria and decrease in urine osmolality was investigated in female WAG/Rij rats free of kidney disease. In these animals, urine osmolality dropped from 2000 mosmol/kg H 2O to 1000–1200 mosmol/kg H 2O between 10 and 30 months, and urinary volume increased in proportion. Vasopressin concentration measured in plasma withdrawn from conscious, unrestrained, chronically catheterized rats was not significantly different in 10, 20 and 30-month-old animals (mean values 2.5 ± 0.7, 2.2 ± 0.2 and 2.0 ± 0.3 pg/ml ( n = 8), respectively). This suggest an impaired responsiveness of old kidney to antidiuretic hormone. The possible involvement of Henle's loop in this defect was studied by micropuncture. Paired collections of tubular fluid were done in the early distal and late proximal convolutions of the same cortical nephrons. Single nephron filtration rates did not significantly differ with age. Tubular fluid osmolalities in the early distal convolution were 165 ± 13, 178 ± 9 and 160 ± 11 ( n = 14) mosmol/kg H 2O in 10-, 20- and 30-month-old rats, indicating similar diluting capacity of the cortical thick ascending limb. The amount of sodium transported from lumen to peritubular space by Henle's loop was also unchanged with age as were water, calcium, magnesium and potassium reabsorptions. These data indicate that the age-related decrease in urine osmolality is not related to either a significant reduced vasopressen plasma concentration or an increa single glomerular sed filtration rate or a reduced transport capacity of Henle's loop of the cortical nephron. Rather they suggest an impaired response to vasopressin of other segments of the nephron that is, the medullary thick ascending limb of Henle's loop and/or the collecting duct.

Role of vasopressin in cardiovascular responses to acute and chronic hyperosmolality

Experiments were performed in conscious chronically instrumented rats to determine the role of arginine vasopressin (AVP) in the cardiovascular adjustments to acute and chronic increases in plasma osmolality. Animals were implanted with pulsed Doppler flow probes and arterial and venous catheters for the determination of cardiac output, mean arterial blood pressure (MABP), and heart rate and for the calculation of total peripheral resistance and baroreflex sensitivity (BRS). Before and after raising plasma osmolality by either 48-h water deprivation or acute hypertonic saline infusion, specific V1- or V2-vasopressinergic receptor antagonists or vehicle were administered to the animals, and the cardiovascular responses were noted. MABP was significantly elevated in water-deprived animals. These animals also exhibited significantly increased BRS, which was further increased by administration of the V1-receptor antagonist. Animals subjected to acute hypertonic saline infusion also demonstrated increased MABP, although the infusion, unlike water deprivation, did not affect BRS. We observed no significant effects on any other variable measured. We conclude that AVP plays a relatively minor role in the cardiovascular adjustments to acute and chronic hyperosmolality.

The role of vasopressin and atrial natriuretic factor in postoperative fluid retention after the Fontan procedure

The Fontan procedure results in right atrial distention and is complicated by fluid retention. Since systemic fluid balance may be hormonally mediated in part and related to right atrium size, we measured plasma atrial natriuretic factor and plasma arginine vasopressin levels in 19 patients undergoing the Fontan procedure and in 12 control patients undergoing other types of heart operations. Preoperative plasma atrial natriuretic factor levels were higher in patients undergoing the Fontan procedure than in control patients (95 +/- 16 pg/ml preoperatively versus 50 +/- 8 pg/ml; p less than 0.05) and increased in patients undergoing the Fontan procedure to 330 +/- 48 pg/ml by postoperative day 2 (p less than 0.05) but not in control patients. Increased plasma atrial natriuretic factor levels could enhance capillary transudation, but elevated plasma atrial natriuretic factor levels should also enhance diuresis and prevent fluid retention. Vasopressin levels, however, were also increased in patients undergoing the Fontan procedure (from 9 +/- 2 pg/ml preoperatively to 144 +/- 37 pg/ml at end of operation) and were higher and remained elevated longer than in control patients undergoing heart operations (37 +/- 7, 20 +/- 4, 16 +/- 6 pg/ml on postoperative days 1, 2, and 3 to 10 for the Fontan group compared with 15 +/- 4, 4 +/- 1, 4 +/- 2 pg/ml for control patients). Vasopressin levels were highest in the Fontan group with the most severe fluid retention and effusions (for example, 51 +/- 10 pg/ml versus 23 +/- 4 pg/ml, on postoperative day 1). Increased vasopressin and atrial natriuretic factor could act synergistically to result in the development of effusions after the Fontan procedure when atrial natriuretic factor-induced capillary transudation is combined with vasopressin-induced antidiuresis.

The role of vasopressin in the pathogenesis of ethanol-induced gastric hemorrhagic erosions in rats: Is vasopressin an endogenous aggressor toward the gastric mucosa?

The role of vasopressin in the development of gastric hemorrhagic erosions induced by the oral administration of 1 mL of 75% ethanol in rats was studied. The area of the lesions in homozygous Brattleboro rats, having a defective vasopressin synthesis, was only 20% of that found in Wistar and heterozygous Brattleboro rats, which have normal vasopressin production. It is well known that vasopressin acts via the V1 (presser) and V2 (antidiuretic) receptors. Administration of V1 and V2 vasopressin-receptor agonists and antagonists in this model showed that pressor-receptor activity is needed for the generation of all lesions in Wistar and heterozygous Brattleboro rats. Ethanol damage to the gastric mucosa was diminished by the V1 antagonist with similar efficacy as in the case of a vasopressin deficiency. Administration of the V1 antagonist and the absence of endogenous vasopressin were shown to protect the deeper layer of the gastric mucosa (assessed by histology) and to reduce significantly the ethanol-induced vascular injury and increase in vascular permeability (assessed by the monastral blue technique). Thus, endogenous vasopressin is clearly of great importance in the pathogenesis of gastric hemorrhagic lesions induced by ethanol. These results strongly suggest that vasopressin is an endogenous aggressor toward the gastric mucosa.

The Backstage Story of the Discovery of LHRH

During my postdoctoral years (1956-1961) spent first at Yale University and then at Tulane University, I was fortunate to become acquainted with many talented endocrinologists. At that time, my major interest was the role of vasopressin in stimulating ACTH secretion. Vasopressin was then one of the strongest candidates for CRF, as advocated by Don McCann. Roger Guillemin and Andrew Serially claimed the existence of separate CRF-a and CRF-β molecules. At Tulane University I worked with Joseph Dingman in the Department of Medicine where I tried to establish a method for separating vasopressin from human plasma using glass fiber paper chromatography. In 1960, on the way home from Miami after attending the Annual Endocrinology Meeting, I happened to board the plane with Schally. He showed a considerable interest in the chromatographic method on which I was working. We talked enthusiastically about CRF and he emphatically denied the possibility that vasopressin was CRF. During my stay in New Orleans, I visited...

Role of vasopressin in clinical hypertension and congestive cardiac failure: interaction with the sympathetic nervous system

The pressor action of vasopressin (AVP) in humans was investigated with the specific anti-vasopressor V1 antagonist d(CH2)5-O(Me)-Tyr-AVP. A single 0.5-mg intravenous bolus of this agent inhibited the pressor effect of AVP by about 80%. Normally hydrated humans had no blood pressure response to this dose, but this agent did prevent the blood pressure rise in response to exogenous AVP given in doses up to 200 milli-units/kg. Patients with severe hypertension, especially that associated with end-stage renal disease, tended to respond with moderate increases in blood pressure and plasma AVP after sodium overload and had a modest blood pressure fall (10-20 mmHg) in response to a single intravenous bolus of the AVP antagonist. Patients with an impaired sympathetic nervous system had increased sensitivity to the pressor action of AVP, in keeping with knowledge derived from experimental studies. These data suggest an interaction between AVP and alpha-adrenergic function, whereby the latter tends to attenuate the pressor action of AVP although it facilitates the release of AVP in response to various stimuli. In patients with congestive heart failure, the direct pressor action of AVP appears to contribute to increased systemic vascular resistance in about 30% of cases, i.e., those with plasma AVP concentrations well above the normal range. In these subjects, circulating AVP concentrations correlated with a decrease in vascular resistance in response to the V1 antagonist.

Role of vasopressin in acutely altered baroreflex sensitivity during hemorrhage in rats

Experiments were performed to examine the potential role of circulating arginine vasopressin (AVP) on baroreflex sensitivity during hypotensive and nonhypotensive hemorrhage in the conscious rat. Animals were chronically instrumented for measurement of cardiac output, blood pressure, and heart rate (HR). Three potential stimuli for release of AVP were utilized: 1) rapid 20% arterial hemorrhage that resulted in hypotension, 2) nonhypovolemic hypotension induced by intravenous infusion of nitroprusside, and 3) nonhypotensive hemorrhage (rapid 10% arterial blood withdrawal). Hypotensive hemorrhage was associated with significant reductions in blood pressure, cardiac output, HR, and calculated total peripheral resistance, an increase in baroreflex (BRR) bradycardia in response to pressor infusions of phenylephrine, and a moderate elevation in circulating AVP. Prior intravenous administration of a specific V1-vasopressinergic antagonist augmented the hypotensive response to hemorrhage; however, neither V1- nor V2-blockade affected hemorrhage-induced augmentation of the BRR. Inducement of hypotension by infusion of nitroprusside did not alter subsequent BRR sensitivity. Finally, nonhypotensive hemorrhage was associated with an increase in resting HR and augmented BRR sensitivity. However, in contrast to hypotensive hemorrhage, either V1- or V2-antagonism attenuated the increase in BRR sensitivity seen with 10% hemorrhage. These data suggest that, although AVP may play a role in blood pressure maintenance via its direct vasoconstrictor actions during hypotensive hemorrhage, the observed augmentation of BRR sensitivity associated with severe blood loss is not attributable to a vasopressinergic mechanism activated by circulating AVP. However, blood-borne AVP may contribute to BRR sensitivity alterations in response to mild blood loss.

A Role for Vasopressin in the Stress‐Induced Inhibition of Gonadotrophin Secretion: Studies in the Brattleboro Rat

Abstract The effects of stress on the secretion of adrenocorticotrophin, corticosterone and luteinizing hormone (LH) in rats congenially lacking hypothalamic vasopressin (Brattleboro rats) and in normal controls of the parent strain (Long Evans) have been compared in an attempt to examine the role of vasopressin in the stress-induced depression of gonadotrophin secretion. In the Long Evans rats, stress (0.6 mg/100g histamine, ip) initiated, within 5 and 20 min respectively, significant (P <0.01, Student's t-test) increases in the plasma adrenocorticotrophin and corticosterone concentrations. It also caused a reduction in the serum LH concentration which was maximal at 5 min. By contrast, in the vasopressin deficient Brattleboro rats, stress had no effect on the serum LH concentration and produced only modest increases in pituitary adrenocortical activity compared with those in Long Evans controls. Pretreatment of both Long Evans and Brattleboro rats with dexamethasone (20mug/100 g ip, daily for 3 days) effectively abolished the pituitary-adrenal response to stress. The steroid treatment also prevented the stress-induced suppression of LH in the Long Evans rats; indeed, these animals, unlike the vehicle-treated controls, exhibited a rise in serum LH concentration within 5 min of exposure to stress. Stress did not affect the serum LH concentrations in steroid-treated Brattleboro rats. The results confirm previous reports that vasopressin is required for the full expression of the pituitary-adrenocortical response stress. They also provide novel evidence which suggests that vasopressin released in stress contributes to the impairment of gonadotrophin secretion.

Role of vasopressin in salt-induced hypertension in baroreceptor-denervated uninephrectomized rabbits.

To elucidate the contributions of renal, humoral, and arterial baroreceptor reflex components to salt-induced hypertension, we administered 10% NaCl intravenously for 10 days to sinoaortic-denervated rabbits with unilateral nephrectomy (n = 7), sinoaortic-denervated rabbits with intact kidneys (n = 7), and sham-operated sinoaortic-denervated rabbits with unilateral nephrectomy (n = 7). Serial changes in mean arterial pressure (MAP), heart rate, and blood pressure variability were recorded. In sinoaortic-denervated rabbits with unilateral nephrectomy, MAP increased significantly from 109 +/- 2 to 124 +/- 3 mm Hg (day 4) and remained elevated for the rest of the experiment. This elevation of MAP was accompanied by a reduction in the standard deviation of MAP, with significant elevations in plasma vasopressin, norepinephrine, and atrial natriuretic peptide concentrations and in sodium retention. In the other groups, there were no significant changes in these vasoactive hormones. In the sham-operated sinoaortic-denervated rabbits with unilateral nephrectomy, sodium retention was similar to that of sinoaortic-denervated rabbits with unilateral nephrectomy. Continuous infusion (1 microgram/kg/hr) of a V1 antagonist prevented the elevation of blood pressure and plasma norepinephrine, the accumulation of sodium, and the reduction of blood pressure lability, whereas a bolus injection (10 micrograms/kg) on day 4 reduced blood pressure from 128 +/- 3 to 115 +/- 2 mm Hg (p less than 0.005). These results imply that vasopressin plays a crucial role in the expression of salt-induced hypertension in rabbits with compromised baroreceptor and renal function.

Role of Vasopressin in Rats with Bilateral Ureteral Obstruction

After unilateral release of bilateral ureteral obstruction (BUO), there is a significant increase in renal vasoconstriction that accounts for the marked decrease in glomerular filtration rate and effective renal plasma flow seen in this setting. We examined the potential role of antidiuretic hormone (ADH), a vasoconstrictor of the renal circulation, on renal hemodynamics in female Sprague-Dawley rats with BUO of 24-hr duration. Rats with BUO had significantly higher plasma values of ADH 65.1 +/- 12.2 vs. 12.1 +/- 4.1 pg/ml), sodium (145.4 +/- 0.91 vs 138.6 +/- 1.06 mEq/liter), and osmolality (375.6 +/- 2.0 vs 310.1 +/- 3.6 mOsm/kg) than sham-operated rats. Rats with BUO pretreated with enalapril, an angiotensin-converting enzyme inhibitor, before obstruction had somewhat higher, but not significantly different, plasma values for ADH (84.6 +/- 20.8 pg/ml) than rats with BUO not given enalapril. Rats with unilateral ureteral obstruction of 24-hr duration had plasma levels of ADH (8.2 +/- 1.3) not different from those in sham-operated rats. Rats with BUO pretreated with a specific antagonist of the V1-type receptor for ADH had significantly greater values for the glomerular filtration rate (2.31 +/- 0.24 vs 1.44 +/- 0.08 ml/min/kg body wt) and the effective renal plasma flow (8.95 +/- 0.71 vs 3.81 +/- 0.44 ml/min/kg body wt) and significantly lower values for mean arterial pressure (140.3 +/- 2.0 vs 159.1 +/- 5.5 mm Hg) than did BUO rats not given the antagonist. The results indicate that high levels of ADH play an important role in the decrease in the glomerular filtration rate and effective renal plasma flow observed in rats with BUO of 24 hr. The significant increase in ADH levels after BUO of 24-hr duration may be due to an increase in osmotic stimulation as a consequence of hypernatremia. Activation of the renin-angiotensin axis, known to occur after BUO or unilateral ureteral obstruction of 24-hr duration, does not appear to have a role in the increased circulating levels of ADH.

Mechanisms of vasopressin's anorectic effect

The present experiments investigated the effect of vasopressin (VP) on food intake in rats under various conditions. VP (1.25–10 μg/kg body weight = b.wt.) injected intraperitoneally (IP) at the onset of the dark phase of the lighting cycle inhibited feeding in a dose-dependent manner. The suppression of feeding induced by VP was primarily due to a delayed onset of the first meal after injection and was reversed by a V 1-receptor antagonist (7 μg/kg b.wt., IP), by the Ca ++-channel blocker verapamil (5 mg/kg b.wt., IP) and by the α-adrenergic receptor antagonist phentolamine (500 μg/kg b.wt.), but not by dissection of the hepatic branch of the vagus. In further experiments VP inhibited gastric emptying. This effect was not reversed by phentolamine. VP had also an aversive effect, but this effect was weaker than that of LiCl and probably not involved in VP-induced hypophagia. The results suggest that VP reduces feeding through a V 1-receptor-mediated activation of an α-adrenergic mechanism. The inhibition of gastric emptying or a possible stimulation of hepatic oxidative metabolism by VP seems to be not essential for VP's effect on feeding. The results are consistent with a role of VP in stress-induced anorexia in rats.

Vasopressin is involved in renal effects of high-protein diet: study in homozygous Brattleboro rats

The present study was designed to test the possible role of vasopressin in the renal response to dietary protein. This possibility was suggested by the similarity of effects on renal function and morphology of chronic high-protein intake and chronic stimulation of urine concentration. Adult male Brattleboro rats, genetically unable to produce vasopressin, were fed high-protein (32% casein = HP, n = 8) or low-protein (10% casein = LP, n = 9) diet for 7 wk. Renal function was evaluated by clearance techniques based on 24-h urine collections in metabolic cages. The response to a single injection of the vasopressin analogue 1-desamino-8-D-arginine vasopressin (DDAVP) was also tested. Kidney weight and height of the different renal zones were assessed at the end of the study. HP diet increased urea excretion nearly sevenfold. Water intake increased by 57% (P less than 0.001) and urine flow rate by 71% (P less than 0.01). Urine osmolality rose from 104 to 181 mosmol/kgH2O (P less than 0.001). At variance with what occurs in rats with endogenous vasopressin (Sprague-Dawley; Bouby, N., et al. Kidney Int 34: 4-12, 1988), HP diet increased creatinine clearance per unit body weight by only 14% and did not change free water clearance, renal mass, and height of inner stripe of outer medulla. However, the rise in urine osmolality and drop in free water clearance after DDAVP were significantly greater in HP- than in LP-fed Brattleboro rats.(ABSTRACT TRUNCATED AT 250 WORDS)