Central vasopressin blockade enhances its peripheral release in response to peripheral osmotic stimulation in conscious rats.

Increased plasma osmolality results in increased central as well as peripheral release of vasopressin. Experiments were carried out to determine whether, in this circumstance, vasopressin can act centrally to modulate its peripheral release. Prior to the start of a thirty-min i.v. infusion of 2.5 M or 0.15 M NaCl, the rats were given an intracerebroventricular (i.c.v.) injection of a peptide V1/V2 vasopressin antagonist (2 micrograms), OPC-31260 (60 micrograms), a non-peptide V2 antagonist, or 1-desamino-8-D-arginine vasopressin (dDAVP, 5 ng), a V2 agonist. Experiments with the peptide antagonist were carried out in male and non-estrous female rats. Since there were no differences between males and females in the measured responses, experiments with the other two drugs were carried out only in males. Pretreatment with either the V1/V2 antagonist or the V2 antagonist enhanced the increase in plasma vasopressin levels in response to the hypertonic saline infusion by about 50% at the end of 30 min. dDAVP, on the other hand, had no effect. None of the i.c.v. drugs had an affect on either the pressor or bradycardic responses to hypertonic saline infusion. These observations suggest that vasopressin can act centrally in a negative feedback fashion to attenuate its own release into the peripheral circulation in response to increased plasma osmolality.

Hypothalamic knife cuts alter fluid regulation, vasopressin secretion, and natriuresis during water deprivation.

To investigate central neural pathways involved in release of vasopressin and in fluid electrolyte regulation, a retractable wire knife was used to make coronal knife cuts posterior to the organum vasculosum lamina terminalis (OVLT). 4 days following cuts or control surgery, animals were housed in metabolism cages and: (1) deprived of food and water for 48 h; (2) deprived of water only for 48 h; or (3) allowed continuous access to food and water. Water ingestion, food ingestion, urine volume, sodium excretion and urine osmolality were recorded daily. Trunk blood was then collected following decapitation for determination of plasma vasopressin, sodium, and protein concentrations, and osmolality. Animals with knife cuts and ad libitum access to food and water had significantly higher plasma osmolality (310 +/- 2 mosm/kg), and plasma vasopressin concentration (2.02 +/- 0.5 microunits/ml) than controls (306 +/- 1 mosm/kg and 0.60 +/- 0.04 microunits/ml, respectively). When rats were deprived of both food and water, there were no significant differences between the two groups in plasma vasopressin concentration, although plasma osmolality wa higher in animals with cuts. However, rats with knife cuts deprived of water only had significantly higher plasma osmolality (358 +/- 8 mosm/kg), sodium (164 +/- 19 mEq/l) and vasopressin (17.7 +/- 4 microunits/ml), than similarly treated control animals (317 +/- 1 mosm/kg, 145.5 +/- 1.0 mEq/1, 5.5 +/- 3 microunits/ml, respectively). These data indicate that a neural pathway in this brain region is critical for normal fluid and electrolyte balance during ad libitum access to food and water, and during water deprivation.

Antidiuresis and inhibition of PGE2 excretion by hyperoxia in the conscious dog.

Experiments were performed to determine the influence of varying inspired oxygen tension on renal prostaglandin E2 (PGE2) excretion, renal hemodynamics, and water and electrolyte excretion in the conscious dog. Hypoxic exposure (PIO2 = 56 torr) resulted in a 13% increase in renal blood flow (RBF), while hyperoxic breathing with PIO2 of 700, 1426, or 2139 torr, all resulted in significant 5--7% decline in RBF, a response that was significantly attenuated compared to the striking renal vasoconstriction caused by hyperoxia in anesthetized dogs. Hyperbaric oxygenation (HBO) (1426 torr O2, 2139 torr O2) was associated with unexpected decreases in urine flow (V) of 61% and 70%, respectively. The antidiuresis and mild hemodynamic adjustments were correlated with a 67% decline in urinary PGE2 excretion (UPGE2 x V) when the dogs breathed 700 torr O2, while exposure to 1426 torr O2 and 2139 torr O2 diminished UPGE2 x V by 92% and 99%, respectively. Plasma antidiuretic hormone (ADH) concentration, measured during exposure to 1426 torr O2, was unchanged. In addition, this nonpharmacologic hyperbaric decline in PGE2 excretion was not associated with any changes in sodium excretion of renin secretion, in contrast to the usual depression of these variables with pharmacologic PG inhibition (indomethacin). The HBO antidiuresis may be a consequence of an increased medullary osmotic gradient secondary to reduced vasa recta blood flow. Alternatively, this antiduresis could occur as a consequence of a lowering of the normal functional antagonism existing between PGE2 and ADH, such that the influence of endogenous ADH is potentiated.

The importance of vasopressin in the development and maintenance of DOC-salt hypertension in the rat.

Experiments were performed to determine the role of vasopressin in deoxycorticosterone (DOC)-salt hypertension. In order to determine if vasopressin is necessary for the development of DOC-salt hypertension, rats with hereditary diabetes insipidus (DI) and normal Long-Evans rats (LE) were unilaterally nephrectomized, treated with DOC Pivalate (30 mg/kg . week) and given saline to drink for 8 weeks. A second group of DI rats were unilaterally nephrectomized, but received no treatment. Systolic blood pressure (SBP) increased 40 mm Hg in the LE group (p less than 0.01) but failed to increase significantly in either DI group. Urinary excretion of vasopressin (UADHV) and SBP were measured in unilaterally nephrectomized LE rats treated with DOC and salt (DOC-LE), salt alone (NaCl-LE) and untreated rats (H2O-LE). The UADHV was elevated in DOC-LE (p less than 0.01) and NaCl-LE (p less than 0.05), but only the DOC-LE rats became hypertensive. Finally, the I.V. injection of analogs of vasopressin, which block its pressor but not antidiuretic activity, lowered mean arterial blood pressure 27 +/- 5 mm Hg in 11 conscious DOC-salt hypertensive rats. It is concluded that vasopressin plays a major role as a pressor agent in both the onset and maintenance of DOC-salt hypertension.