Ewa Szczepańska-Sadowska

Hemodynamic effects of moderate increase of the plasma vasopressin level in conscious dogs

SummaryThe influence of moderate increase of the plasma ADH level on aortic and central venous pressures, heart rate, cardiac output, stroke volume, central blood volume, systemic peripheral resistance and plasma volume was examined in conscious dogs. The animals were given 0.75 mU ADH/kg b.w. in single intravenous injection as a priming dose. This was followed by a constant infusion of the hormone at a rate of 0,12 mU/min/kg/0.2 ml 0.9% NaCl solution lasting one hour. Plasma ADH level measured at 30 min of the infusion was equal to 22 ± 4 μU/ml. A significant increase of aortic (mean systolic and diastolic) and central venous pressures, systemic peripheral resistance and of plasma volume was observed in the course of the infusion. It was accompanied by a decrease of heart rate, cardiac output and central blood volume. Changes of stroke volume were not significant.As the plasma level produced by the infusion was such as that following a moderate nonhypotensive haemorrhage [30], the rôle of the hemodynamic effects of vasopressin in maintenance of the blood pressure and volume in hypovolemia is discussed.

Plasma and cerebrospinal fluid vasopressin and osmolality in relation to thirst

Conscious dogs chronically implanted with a device for cerebrospinal fluid (CSF) sampling from the anterior 3rd ventricle were submitted to 24 h dehydration. During rehydration by drinking the total water intake (TWI) after 16 min was determined in 8 and after 90 min in 14 experiments. Samples were simultaneously drawn to determine the osmolalities (Posm, CSFosm) and AVP concentrations (PVVP, CSFAVP) of plasma and CSF. After 24 h dehydration all of these parameters were significantly elevated in comparison to euhydrated dogs investigated on 19 occasions. In 8 experiments 60% of the final TWI had been ingested within the first 16 min with no changes of Posm, CSFosm and CSFAVP, but a significant decrease of PAVP at this time. TWI per kg body weight (TWI·kg−1) after 90 min was significantly correlated with the osmolalities and AVP levels in plasma and CSF prior to rehydration. The decreases of Posm, CSFosm and PAVP, but not of CSFAVP, were significantly correlated with TWI·kg−1. The results indicate that PAVP and CSFAVP are subject to long term control by body fluid tonicity exhibiting a feedback relationship to water intake. In addition, PAVP but not CSFAVP seems to be under short term, possibly nonosmotic, control during water intake.

Thirst impairment elicited by intraventricular administration of vasopressin antagonists

To determine whether centrally released vasopressin influences thirst, observations of osmotic thirst threshold, osmotic load excretion and postloading restitution of plasma osmolality were made in dogs in control experiments and during infusion of AVP antagonists into the third ventricle. Significant elevation of osmotic thirst threshold was elicited by infusion of d(CH2)5AVP at a rate of 0.2-2.0 micrograms.min-1 and of d(Et2)AVP at a rate of 0.3 micrograms.min-1 (V1 antagonists, weak V2 agonists) as well as by administration of d(CH2)5[D-Ile2,Abu4]AVP at a rate of 0.4 micrograms.min-1 (potent V2 antagonist, weak V1 antagonist). Administration of d(CH2)5AVP at a rate of 2.0 micrograms.min-1 was associated with a significant suppression of the postloading water intake and osmotic load excretion and with a delay in restitution of plasma osmolality. These findings indicate that centrally released vasopressin may participate in the control of thirst.

The effect of calcium ions chelation and sodium ions excess in the cerebrospinal fluid on body temperature in conscious dogs

SummaryThe effects of chelation of calcium ions and elevation of sodium ions concentration in cerebrospinal fluid on body temperature was examined in conscious dogs. Decrease of calcium ions concentration brought about by an infusion of disodium edetate (Na2EDTA) into the lateral ventricle elicited an increase in body temperature in 8 out of 10 experiments by 1.49±0.36°C. Huddling, piloerection, lowering of respiratory rate, vasoconstriction and shivering occurring in the course and after Na2EDTA infusion argue that hyperthermia resulted both from excess production of heat and activation of heat conservation mechanisms. Two intraventricular infusions of artificial CSF containing 88 mM Na+ in excess of its physiological concentration did not produce any effect on body temperature.The role of calcium ions concentration in brain centres regulating body temperature is discussed.

The activity of the hypothalamo-hypophysial Antidiuretic system in conscious dogs

SummaryThe influence of isoosmotic changes of blood volume on the plasma vasopressin level, osmotic reactivity of the antidiuretic system, arterial blood pressure, central venous pressure and heart rate was examined in 13 conscious intact dogs. The rate of disappearance of exogenous vasopressin under control conditions and during hypovolemia was also investigated. A moderate decrease of blood volume produced a clear cut and persistent increase of the plasma vasopressin level, and a fall of central venous pressure. The same blood loss did not change the rate of disappearance of vasopressin from the plasma.Moderate blood volume expansion produced a decrease of plasma ADH level and of the osmotic reactivity of the antidiuretic system. Hypervolemia produced a marked increase of central venous pressure and central blood volume.The result suggest that moderate changes of blood volume modify the activity of the hypothalamo-hypophysial antidiuretic system and support the hypothesis of Gauer and Henry (see [7]) that impulses influencing the activity of the hypothalamo-hypophysial antidiuretic system arise in the central low-pressure part of the circulatory system.

Osmotic thirst suppression during 2,4-dinitrophenol (DNP) hyperthermia in the dog

SummaryThe effect of generalized body hyperthermia elicited by intravenous infusion of 2,4-dinitrophenol (DNP) on the reactivity of the thirst mechanism to osmotic stimuli was examined in conscious dogs.DNP increased deep body temperature by 1.53±0.18° C in 18 out of 20 experiments. Impairement of thirst sensation was observed at the same time. The animals did not drink enough water to compensate for its total and evaporative loss. In consequence water deficit developed, reaching maximum value of 2.7±0.6% of body weight. The deficit was accompanied by an increase in plasma osmolarity, plasma protein concentration and hematocrit. A significant correlation between evaporative water loss and water deficit as well as between increase in deep body temperature and water deficit was found.The cellular dehydration developed in the course of DNP hyperthermia was higher by 3.3±0.6% of intracellular water (P<0.001) than that which was necessary to elicit drinking under conditions of normothermia.It is concluded that DNP hyperthermia changes the osmotic reactivity of the thirst mechanism so that the body fluids osmolarity is regulated at a higher level. This finding is discussed with regard to voluntary dehydration.

Antagonistic effects of vasopressin and hypervolemia on osmotic reactivity of the thirst mechanism in dogs

SummaryThe reactivity of the thirst mechanism to osmotic stimuli was examined in conscious dogs 1. under control conditions, 2. after raising the plasma vasopressin (PADH) level to about 30 μU/ml by intravenous infusion of the hormone, 3. after expansion of the blood volume by 15% by an intravenous infusion of dextran solution, and 4. after a simultaneous increase ofPADH and blood-volume expansion.The osmotic thirst threshold was significantly lowered by the elevation ofPADH and augmented by an expansion of blood volume, whereas no significant changes were observed when the increase inPADH and expansion of blood volume were applied simultaneously.The interactions between body-fluid osmolarity, blood volume, and vasopressin in regulation of water intake are discussed.

Equipotency of hypertonic solutions of mannitol and sodium chloride in eliciting thirst in the dog

SummaryThe dogs were infused intravenously with either 3.6% NaCl or 20% mannitol solutions. Both infusions stimulated the animals to drink water when similar osmotic loads were introduced and exactly the same degree of cellular dehydration achived. The amounts of water drunk at thirst threshold did not differ significantly.The results are discussed with relation to the hypothesis of osmometric control of water intake.

The effect of barbiturates on 24-h water intake and renal excretion of sodium and water in dogs (1)

The effects of barbiturates on 24-h intakes of water and food and urinary excretion of sodium and potassium as well as on plasma concentration of sodium and potassium and osmolality were examined in dogs placed in metabolism cages and fed with a semiliquid diet. Administration of barbiturates stimulated drinking in a Series of 8 dogs having free access to water. Twenty four-h water intake and water balance increased significantly. Food intake, urinary output and urinary excretion of solutes, sodium and water did not change in this Series. A significant decrease in urine output as well as in osmolal clearance and urinary excretion of sodium was observed in a Series of 7 dogs having water restricted for 24 h following administration of barbiturates. Water balance increased in this Series. The same restriction of water in the dogs which had not received barbiturates did not modify renal excretion of water and electrolytes. Plasma osmolality, sodium and potassium concentrations did not change in either Series of experiments. It is concluded that barbiturates induce positive water balance either by stimulation of drinking when water is freely available or by reduction in urine output when water is restricted. The results suggest that expansion of the body fluids following the increased water intake may abolish reduction in urine output and sodium excretion which otherwise occur after administration of barbiturates.

Osmotic Thirst Suppression after Central Administration of Vasopressin Antagonists

We have previously reported that administration of vasopressin (AVP) to the third ventricle (3rdV) stimulates intake of water in normally hydrated dogs1. It has been also found that concentration of AVP in the cerebrospinal fluid (CSF) changes in parallel to body fluid osmolality2,3. The present study was aimed at elucidating whether centrally released endogenous AVP may be of physiological significance for the control of the osmotic thirst. To this end the osmotic thirst threshold and the postthreshold intake of water as well as restitution of plasma osmolality were determined under control conditions and after administration of competitive antagonists of AVP.