Impaired ability to excrete a water load occurs in a substantial number of patients with advanced cirrhosis and in animals with experimental cirrhosis. The nonosmotic stimulation of arginine vasopressin release from the pituitary has been implicated as an important factor in the abnormal water excretion in patients and animals with cirrhosis. In this study, arginine vasopressin hypothalamic gene expression was studied in cirrhotic rats. Cirrhosis was induced by a combination of phenobarbital treatment in drinking water and weekly intragastric administration of carbon tetrachloride for 13 to 15 wk. Severe cirrhosis was confirmed by morphological analysis and the presence of ascites. Plasma arginine vasopressin was also significantly higher in rats with cirrhosis (control = 1.77 +/- 0.16 and cirrhotic rats = 4.14 +/- 0.62 pg/ml, n = 9, p < 0.002). Hypothalamic arginine vasopressin messenger RNA was also significantly higher in cirrhotic rats (control = 762.1 +/- 132.3 and cirrhotic rats = 1,834.2 +/- 271.9 pg/hypothalamus, n = 9, p < 0.005). Pituitary arginine vasopressin content was significantly lowered in cirrhotic rats (control = 3.69 +/- 0.98 and cirrhotic rats = 1.57 +/- 0.09 micrograms/pituitary, n = 9, p < 0.05). No difference was seen in hypothalamic arginine vasopressin content between the two groups (control = 4.64 +/- 0.34 and cirrhotic rats = 4.23 +/- 0.33 ng/hypothalamus, n = 9, NS). Oxytocin messenger RNA in the hypothalamus was also not significantly different between the two groups (control = 8.61 +/- 0.68 and cirrhotic rats = 9.33 +/- 0.65 unit of density, n = 9, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

The present study was undertaken to examine vasopressin gene expression in response to a normal versus hypertonic sodium chloride (506 mOsm/kg H2O) intake for 7 days in Sprague-Dawley rats. The animals in both groups demonstrated precision in maintaining constancy of body fluid composition in spite of large differences in sodium and water intakes. Compared with the rats on a normal diet, chronic ingestion of hypertonic sodium chloride resulted in significant increases in total fluid intake (210 +/- 8 mL v 471 +/- 48 mL, P < 0.001) and total urine output (86 +/- 5 mL v 347 +/- 48 mL, P < 0.001), while glomerular filtration rate, hematocrit, serum urea nitrogen, creatinine, serum sodium, and plasma osmolality were unchanged. Without detectable changes in plasma osmolality or intravascular volume, vasopressin release from the pituitary, as measured by plasma and pituitary vasopressin concentrations (1.5 +/- 0.1 pg/mL v 5.9 +/- 1.5 pg/mL, P < 0.01 and 2.0 +/- 0.5 micrograms/pituitary v 0.86 +/- 0.1 micrograms/pituitary, P < 0.01, respectively), was increased in the animals ingesting hypertonic sodium chloride. In addition, vasopressin gene expression as measured by hypothalamic vasopressin mRNA concentrations was significantly increased 1.85-fold (P < 0.001) in the animals ingesting hypertonic sodium chloride. In summary, Sprague-Dawley rats ingesting hypertonic sodium chloride (506 mOsm/kg H2O) were able to maintain sodium and water homeostasis over a 7-day period. Yet, in these animals plasma vasopressin increased, pituitary vasopressin stores decreased, and hypothalamic vasopressin gene expression was stimulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothyroidism is associated with abnormalities in renal water handling, which include a delay in excretion of an acute water load, decreased urinary concentrating ability, and increased urine volume. In the present study, we investigated the role of vasopressin in aminotriazole-induced hypothyroidism by measuring vasopressin concentration in the plasma and pituitary along with vasopressin mRNA levels in the hypothalamus. After 5 weeks of aminotriazole treatment, L-thyroxine levels were significantly lower in the experimental animals (122 +/- 8 v 26 +/- 1 nmol/L [9.5 +/- 0.6 v 2.0 +/- 0.1 micrograms/dL]; P less than 0.001). Serum sodium (148 +/- 0.5 v 144 +/- 1.2 mmol/L [mEq/L]; P less than 0.01), and plasma osmolality (311 +/- 2.5 v 304 +/- 1.8 mmol/kg [mOsm/kg] H2O; P less than 0.05) were also lower in the experimental animals. There were no differences in plasma (1.9 +/- 0.4 v 1.5 +/- 0.2 pg/mL) or pituitary (1.5 +/- 0.4 v 1.5 +/- 0.2 microgram/pituitary) vasopressin levels. In addition, steady-state vasopressin mRNA levels were not different between the two groups (1,286 +/- 210 v 1,093 +/- 138 pg/hypothalamus). One week of L-thyroxine replacement resulted in significant increases in serum thyroxine levels without changes in the other variables measured. These results indicate that short-term hypothyroidism, which has been shown to exert substantial effects on renal function, causes only a modest central alteration in the plasma vasopressin-osmolality relationship, which occurs in the absence of detectable changes in vasopressin synthesis.

We reviewed our 115-month experience with continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD) in adult and pediatric patients to determine whether there is a difference in the incidence of peritonitis between patients performing CAPD or CCPD. Peritonitis rates were similar in patients performing CAPD or CCPD in both the adult and pediatric age groups. The overall CAPD peritonitis rate was significantly lower in adult patients when compared with pediatric patients. There was no difference in peritonitis rates for CCPD between adult and pediatric patients. When the data are divided into 3-year subgroups, the incidence of peritonitis is significantly lower in adult patients undergoing either CAPD or CCPD when compared with pediatric patients during the years 1986 to 1988. There is significant improvement over time in the incidence of peritonitis in both adult and pediatric patients performing CCPD; similarly, there is a trend toward improvement in patients performing CAPD. Staphylococcus species organisms remain the most common bacterial cause of peritonitis, except in pediatric patients under the age of 2 years or with nephrostomies, where gram-negative rod infections were more common. Peritonitis resulted in discontinuation of peritoneal dialysis in a greater number of adult patients. These results suggest that the number of catheter manipulations is not important in determining the incidence of peritonitis. Pediatric patients are more likely than adult patients to develop peritonitis with either CAPD or CCPD. Adult patients are more likely than pediatric patients to discontinue peritoneal dialysis secondary to peritonitis.

Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome, and pregnancy. Nonosmotic vasopressin release has been implicated in the water retention of these edematous disorders. The nonosmotic release of vasopressin is consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems in both experimental animals and in edematous patients. Moreover, the sympathetic nervous system has been shown to be involved in the nonosmotic release of vasopressin and activation of the renin-angiotensin system. These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial resistance. Neither total extracellular fluid volume nor blood volume is a determinant of renal sodium and water excretion. Rather, renal sodium and water retention is initiated by a decrease in effective arterial blood volume (EABV) due to either a fall in cardiac output or peripheral arterial vasodilation. The acute response to a decrease in EABV involves vasoconstriction mediated by angiotensin, sympathetic mediators, and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and aldosterone-mediated sodium retention. The resultant renal vasoconstriction limits the distal tubular delivery of sodium and water, thus maximizing the water-retaining effect of vasopressin and impairing the normal escape from the sodium-retaining effects of aldosterone. The elevated glomerular filtration rate and filtered sodium load in pregnancy allows increased distal sodium and water delivery in spite of a decrease in EABV, thus limiting edema formation during gestation.

Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome and pregnancy. In recent years the use of a sensitive radioimmunoassay for plasma vasopressin has implicated the role of nonosmotic vasopressin release in the water retention of these edematous disorders. In experimental studies and studies in humans it has been found that the nonosmotic release of vasopressin is consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system has been shown to be involved in the nonosmotic release of vasopressin (carotid and aortic baroreceptors) and activation of the renin-angiotensin system (renal beta-adrenergic receptors). These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial resistance. In this context neither total extracellular fluid (ECF) volume nor blood volume are determinants of renal sodium and water excretion. Rather, renal sodium and water retention is initiated by either a fall in cardiac output (e.g. ECF volume depletion, low-output cardiac failure, pericardial tamponade or hypovolemic nephrotic syndrome) or peripheral arterial vasodilation (e.g. high-output cardiac failure, cirrhosis, pregnancy, sepsis, arteriovenous fistulae and pharmacologic vasodilators). With a decrease in effective arterial blood volume (EABV), initiated by either a fall in cardiac output or peripheral arterial vasodilation, the acute response involves vasoconstriction mediated by angiotensin, sympathetic mediators and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and aldosterone-mediated sodium retention. The renal vasoconstriction which accompanies those states that decrease EABV, by either decreasing cardiac output or causing peripheral arterial vasodilation, limits the distal tubular delivery of sodium and water thus maximizing the water-retaining effect of vasopressin and impairing the normal escape from the sodium-retaining effects of aldosterone. The elevated glomerular filtration rate and filtered sodium load in pregnancy allows increased distal sodium and water delivery in spite of a decrease in EABV, thus limiting edema formation during gestation.This review has examined the pathophysiology of vasopressin in the edematous disorders of cardiac failure, cirrhosis, nephrotic syndrome and pregnancy and proposed a unifying hypothesis of body fluid volume regulation. A decrease in the EABV secondary to either a decreased cardiac output or a decrease in peripheral arterial resistance is proposed as the initiator of sodium and water retention. This decreased EABV leads to nonosmotic release of vasopressin and to activation of the sympathetic nervous and renin-angiotensinaldosterone systems. Nonosmotic release of vasopressin leads to water retention while increased secretion of aldosterone, and failure to escape from the hormones sodium-retaining effect, leads to sodium retention in edematous disorders.Exceptions to the above statements may exist in nephrotic syndrome and pregnancy. In nephrotic syndrome, the kidney is diseased and intrarenal mechanisms may lead to expansion of the arterial vascular tree and suppression of the renin-angiotensin-aldosterone system. In pregnancy, the increased glomerular filtration rate and increased distal delivery of sodium and water “aldosterone escape” to occur.