Noradrenergic modulation of avian kidney function.

Norepinephrine (NE) infused at doses of 0.7, 2.2 and 6.7 micrograms/min/kg body weight into conscious, salt and water loaded ducks dose-dependently induced arterial hypertension, reflex bradycardia and diuresis/natriuresis at unchanged glomerular filtration and reduced renal blood flow. NE-induced changes in plasma concentrations of osmoregulatory hormones consisted of a slight increase for the antidiuretic hormone, no change for angiotensin II and a nearly 4-fold increase for atrial natriuretic factor. Sub-pressor doses of NE infused close to the origin of the renal arteries induced diuresis without a rise in urinary sodium concentration. The results suggest pressure diuresis in ducks as a response to hypertensive NE doses with a possible contribution of atrial natriuretic factor to natriuresis.

Disinhibition of AVP release during noradrenaline and angiotensin II infusions in dogs by maintaining normotension with sodium nitroprusside.

Noradrenaline (NA) and angiotensin II (A II) were infused intravenously in conscious dogs without (series I) and with (series II) additional infusions of sodium nitroprusside at doses re-establishing normal levels of mean arterial pressure (MAP). In series I, NA infusion (1.6 micrograms/min per kg for 30 min) initially elevated MAP by some 25 mm Hg and lowered heart rate by some 30 beats/min. Plasma concentrations of arginine vasopressin (AVP) remained constant, while those of A II and atrial natriuretic factor were slightly, but significantly, increased. Infusion of A II (10 or 20 ng/min per kg for 30 min) induced similar rises in MAP and slight reductions of heart rate and increased plasma AVP by 70% and atrial natriuretic factor by 60%. In series II, sodium nitroprusside (1-4 micrograms/min per kg) was added for 30 min to infusions of NE (1.6 micrograms/min per kg) and A II (20 ng/min per kg) in order to maintain MAP at its control level. This resulted in an 11-fold increase in plasma AVP during NA infusion and a 19-fold increase during A II infusion. Infusing sodium nitroprusside (4 micrograms/min per kg) alone lowered MAP to clearly hypotensive levels, but the resulting rises in plasma AVP were less than, rather than equal to, those seen at normotensive MAP levels during the combined infusions of sodium nitroprusside with A II or NA, respectively. It is concluded that both NA and A II exert strong stimulatory actions on AVP release which are, however, counteracted by inhibitory influences arising from the hypertensive effects of NA and A II.

Ionic responsiveness in third ventricular hypertonic stimulation of antidiuresis in ducks.

Domestic ducks were chronically equipped with a device probing the third cerebral ventricle (VIII) for localized intracerebroventricular (i.c.v.) perfusion. In conscious animals made diuretic by intravenous water loading with 1.0 ml/min hypoosmotic glucose solution (200 mOsm/kg), hyperosmotic i.c.v. stimulations were tested for antidiuretic actions. Artificial cerebrospinal fluid made hypertonic (400 mOsm/kg) by adding sucrose, mannitol, NaCl, LiCl, choline chloride, NaI, NaNO3, LiNO3, CaCl2 or MgCl2 was perfused i.c.v. for 10-15 min at rates of 10-15 microliters/min. Arterial pressure and heart rate were monitored continuously. Hyperosmotic stimulations with non-electrolytes did not induce antidiuresis. Approximately equivalent degrees of antidiuresis were elicited by Na(+)-, Li(+)- and choline salts with a tendency for moderate rises in arterial pressure. Compared to Cl(-)- and I(-)-salts, the effects of NO3(-)-salts were attenuated. Divalent cations caused prolonged antidiuresis, sometimes preceded by initial diuresis, with circulatory side effects unrelated to the changes in renal fluid excretion. It is concluded that the observed antidiuretic effects were mediated by cation-sensitive, rather than osmosensitive neurons on the brain side of the blood-brain-barrier. Their transduction mechanism might consist of poorly selective membrane channels permeable to cations but not to anions.

Functional hypothalamic angiotensin II and catecholamine receptor systems inside and outside the blood-brain barrier.

To elucidate the contribution of various hormones and neuromodulators in the central nervous control of body fluid homeostasis, the saltwater-acclimated Pekin duck represents an ideal model due to the cytoarchitecture of its hypothalamus, and the marked systemic and hypothalamic sensitivity of its osmoregulatory system. Employing animal physiology, electrophysiology, histochemistry and receptor binding techniques, the role of angiotensin II (A II) and norepinephrine (NE) as both circulating hormones and neurotransmitters in central osmoregulation through interaction with neuronal targets inside and outside the blood-brain barrier (BBB) could be investigated. Application of both agents into the systemic circulation or into the cerebrospinal fluid of conscious animals, and the monitoring of hypothalamo-neurohypophyseal antidiuretic hormone ADH (= AVT) release, cardiovascular parameters such as mean arterial pressure (MAP) and avian salt gland function allowed to discriminate between actions of A II and NE at sites within or outside the BBB. Of the latter, the median eminence (ME), the subfornical organ (SFO) or the organum vasculosum laminae terminalis (OVLT) are of prime importance. Receptor autoradiography using radioiodinated ligands specific for A II, alpha 1-, alpha 2- and beta-receptors including the pharmacological characterization of these binding sites permit to establish a molecular correlate of the modulatory actions of both A II and NE.

ADH, renal, and circulatory responses to adrenergic stimulation in anterior third ventricle.

The anterodorsal part of the third ventricle of conscious ducks was perfused intracerebroventricularly (icv) for 10 min with norepinephrine (NE) or with its agonists phenylephrine (alpha 1, Phe), isoproterenol (beta, Iso), and clonidine (alpha 2, Clo) in artificial CSF (aCSF). Their effects on the plasma level of antidiuretic hormone (AVT, arginine vasotocin in birds), urine excretion, heart rate (HR), and mean arterial pressure (MAP) were investigated in steady-state water diuresis. The correct position of the icv cannula was confirmed by enhanced AVT release and antidiuresis in response to icv perfusion of aCSF made hypertonic (400 mosmol/kgH2O) by adding NaCl. Icv perfusion with hypertonic aCSF and 750 ng/min NE had comparable effects on AVT release and urine excretion, but hypertonic aCSF caused small increases in MAP and HR, whereas NE depressed both MAP and HR. Antidiuresis and circulatory depression caused by NE icv perfusion was dose dependent. Among the adrenergic agonists perfused at similar doses (188 ng/min), only Iso stimulated AVT release. Iso and Phe had small depressive effects on MAP and HR (less than 10%). Clo depressed circulation by greater than 20% for longer than 60 min, and AVT release became significantly reduced 30 min after the start of icv perfusion. The consistent results in ducks contrast with the equivocal data hitherto reported for central stimulations with NE or its agonists in mammals and may be due to the concentric perfusion system used in our study for localized stimulations in the vicinity of the paraventricular nucleus.

Osmotic and hormonal stimulation of the third ventricular region of ducks: antidiuretic, circulatory and local neuronal responses.

By means of local microperfusion of the 3rd cerebral ventricle, antidiuretic and circulatory responses to stimulations with various hypertonic solutions and norepinephrine were analyzed in conscious ducks. The results suggest ionic rather than osmometric responsiveness of periventricular osmoreceptive elements, which is in line with single unit recordings of periventricular neurons tested in vitro for their osmoresponsiveness. These neurons were located subependymally at the site of greatest responsiveness in vivo, and corresponded to morphologically identified neurons projecting to the neuroendocrine hypothalamo-pituitary system. Antidiuresis was combined with increases in arterial pressure and heart rate in response to hypertonic stimulations with monovalent cations; divalent cations produced long-lasting antidiuresis and equivocal circulatory responses. Norepinephrine elicited antidiuresis which was accompanied by arterial hypotension and bradycardia. Osmotically and norepinephrine induced antidiuresis was combined with increases of plasma ADH concentration. Different modulatory actions of intrinsic adrenergic, angiotensinergic and vasotocinergic neurons are suggested in hypothalamic control of autonomic functions.

Occlusion of rostroventral 3rd ventricle abolishes drinking but not AVP release in response to central osmotic stimulation.

Dogs were implanted with a device for chronic cannulation of the anterior part of the 3rd ventricle (A3V). Intracerebroventricular (i.c.v.) infusion of artificial cerebrospinal fluid (CSF) containing 0.35 M NaCl into the A3V of 7 normally hydrated dogs induced thirst (average water intake 11.8 +/- 2.0 ml.kg-1 b. wt.) and significantly increased arginine-vasopressin (AVP) concentration in the blood plasma from 3.4 +/- 0.3 to 8.2 +/- 1.2 pg.ml-1. When repeating the i.c.v. hypertonic infusion at intervals of one week or more in two dogs, its dipsogenic effect vanished within 3-5 months. X-ray analysis revealed an occlusion of the rostroventral part of the A3V. Subsequent controls on 3 other dogs confirmed that the dipsogenic response to i.c.v. osmotic stimulation was abolished in association with similar partial occlusions of the A3V. However, this stimulus still produced a significant increase of plasma AVP from 3.7 +/- 0.5 to 5.7 +/- 0.7 pg.ml-1 in the 5 dogs. Control of drinking in these dogs was otherwise unimpaired as indicated by their normal plasma osmolalities. Histological examination revealed that the loss of the dipsogenic response to i.c.v. infusion of 0.35 M NaCl was in each case associated with fibrinous occlusion of the A3V between its rostral wall and the mass intermedia, preventing the passage of the infusate to the supraoptic and infundibular recesses.

Central and systemic antidiuretic hormone and angiotensin II in salt and fluid balance of birds as compared to mammals.

1. Tonicity dominates the release of ADH with similar sensitivities (0.2-1 pg/ml per mOsm/kg) for both birds and mammals. 2. There is an inverse relationship between the volume of the extracellular fluid compartments and the plasma level of ADH. 3. Angiotensin II formation is governed by volume factors. 4. In birds the factors reducing the delivery of Na+ to the nephron distal tubules stimulate ANGII formation. 5. Mammals have a high vascular constrictor sensitivity to ADH and ANGII; there is little or no vascular sensitivity to these in birds. 6. In birds and mammals the subfornical organ and other circumventricular organs have receptors that specifically bind ANGII. 7. Dog and duck CSF levels of ADH and AII indicate their function as specific mediators of intrinsic neuronal systems controlling salt and fluid balance.

Gradient of arginine vasopressin concentration but not angiotensin II concentration between cerebrospinal fluid of anterior 3rd ventricle and cisterna magna in dogs.

Dogs were chronically implanted with two devices for cerebrospinal fluid (CSF) sampling from (a) the anterior part of the 3rd ventricle and (b) the cisterna magna. In conscious dogs arginine vasopressin (AVP) concentration of CSF samples collected at different occasions were 2-3 times higher in the CSF of the 3rd ventricle as compared to the AVP concentration of the cisterna magna. Inhalation anesthesia stimulated AVP release into the CSF at both sites by a factor of about 2, the gradient between 3rd ventricle and cisterna magna CSF of 2-3 remained for AVP in simultaneously collected samples. In contrast, angiotensin II-like immunoreactivity of CSF was not significantly different at both sites, neither in the conscious dogs nor during anesthesia. It is concluded that the main amount of AVP enters the CSF at the 3rd ventricular level.

Interaction of changes in the third ventricular CSF tonicity, central and systemic AVP concentrations and water intake.

Arginine vasopressin (AVP) is assumed to be involved as a central transmitter or modulator in the control of autonomic functions including thirst. In conscious dogs AVP concentration in cerebrospinal fluid (CSF) from the anterior part of the third ventricle (A3V) was analysed before and after local elevation of CSF osmolality by intracerebroventricular (i.c.v.) infusion of 0.35 M NaCl and after i.c.v. AVP infusion at 46 and 138 fmol ml-1 for 10 min. In addition, the effects of these i.c.v. infusions on water intake, plasma AVP concentration and blood pressure were investigated. In euhydrated dogs 0.35 M NaCl i.c.v. did not alter AVP concentration in the CSF during the subsequent 2 h. In contrast, plasma AVP concentration had increased significantly from 3.4 +/- 0.3 (control) to 6.4 +/- 0.7 and 4.7 +/- 0.3 fmol ml-1, 4 and 16 min, respectively, after the hypertonic stimulus. Drinking was stimulated with an average water intake of 14.5 +/- 3.7 ml kg-1 body wt. However, AVP infusion into the A3V did not elicit water intake despite increases of AVP concentration in the A3V by factors up to 40 above control. The same animals responded with spontaneous drinking to 0.35 M NaCl i.c.v. administered 160 min after the end of AVP infusions. Exogenously administered AVP disappeared from the A3V with a time constant of 13.8 min. The results do not support the view that AVP in the A3V CSF per se stimulates drinking.

Effect of bombesin on thermoregulation of the rabbit.

Injections of bombesin (BOM, 125, 250 and 500 ng) into the preoptic/anterior hypothalamus caused dose-related decreases of threshold temperatures for metabolic cold defence, cutaneous vasomotor tone and respiratory rate, combined with a reduced sensitivity of these thermoregulatory effectors in response to core temperature changes induced at thermoneutral or warm ambient conditions. Intracisternal (i.c.) injections of BOM (250 ng) produced qualitatively identical thermoregulatory effector changes in response to core temperature changes. Injections of BOM into the posterior hypothalamus did not affect body temperature control. Increased locomotor behavior, licking and grooming was elicited, however, from all injection sites. The results explain the prevailing hypothermic effect of BOM as the consequence of the concerted decrease in threshold temperatures and "gains" of all autonomic thermoregulatory effectors and suggest the activation of warm inputs, relative to cold inputs, at the hypothalamic level as the underlying mechanism. Direct or indirect inhibition of the intrinsic hypothalamic system involving thyrotropin-releasing hormone (TRH) and consequent deactivation of central noradrenergic pathways known to generate the entire autonomic pattern of cold defence might be involved in the neuro-humoral changes resulting in hypothermic effects of centrally applicated BOM.

Thermally induced changes in neural and hormonal control of osmoregulation in a bird with salt glands (Anas platyrhynchos).

In conscious Pekin ducks adapted to hypertonic saline (1.9%) as drinking water, steady state secretion of the salt glands was established by continuous intravenous salt loading and the effects of hypothalamic thermal stimulation on salt gland activity and on the plasma concentrations of arginine vasotocin (AVT) and angiotensin II (AII) were observed. Hypothalamic cooling depressed salt gland secretion and the plasma level of AVT. Hypothalamic warming caused transient activation and subsequent inhibition of salt gland secretion without consistent changes of the plasma levels of AVT and AII. Whole body cooling by heat extraction with a colonic thermode produced moderate inhibition of salt gland activity, without changes in plasma AVT and AII, which may be explained by peripheral vasoconstriction. The results are consistent with the view that hypothalamic osmoregulation is under an influence of local temperature by combined osmo/thermo-responsiveness of hypothalamic neurons and temperature dependence of signal transmission in hypothalamic neural integration of osmoregulation.

Independent osmoregulatory control of central and systemic angiotensin II concentrations in dogs.

In 14 dogs angiotensin (ANG II)-like immunoreactivity was analyzed in simultaneously collected samples of cerebrospinal fluid (CSF) from the anterior part of the third cerebral ventricle and of plasma. Plasma and CSF ANG II were not different in euhydrated conscious dogs (29.3 +/- 2.7 and 30.8 +/- 2.8 pg X ml-1, means +/- SE). During anesthesia CSF ANG II was not significantly altered, but plasma ANG II was more than doubled in comparison with conscious animals. In conscious dogs 24 h of dehydration with sodium-rich food significantly increased ANG II concentration in the plasma (to 59.8 +/- 16.5 pg X ml-1) and CSF (to 71.8 +/- 20.1 pg X ml-1). Subsequent rehydration by drinking caused no consistent changes in plasma ANG II within 90 min but reduced CSF ANG II significantly. Salt loading by infusion of 5% saline in seven conscious dogs produced a small but consistent decrease in plasma ANG II by 20%, on average, whereas CSF ANG II rose in five animals. The directions of changes in concentration of central ANG II compared with plasma ANG II suggest that central endogenous ANG II may function as a central osmoregulatory mediator independent from systemic ANG II.

Blood pressure and arginine vasotocin in normonatremic and hypernatremic ducks.

As a model to study effects of chronic, excessive salt loading on circulation, Pekin ducks were adapted to 2% saline solution as their sole water supply, while fresh-water-adapted animals were used as controls. Due to the development of salt-eliminating glands, salt-adapted ducks are able to cope indefinitely with this salt stress which means a daily ingestion of 5-6 g NaCl per kg body weight per day, associated with a chronic elevation of plasma osmolality and plasma sodium by 5-8% above normal and an up to 3-fold increase of antidiuretic hormone concentration in comparison to animals maintained on fresh water. Salt loading for up to 14 months did neither increase arterial mean, nor diastolic, nor pulse pressure. On the contrary, arterial mean and diastolic pressure were slightly lower in the salt-adapted than in the fresh-water-adapted animals, while pulse pressure and heart rate did not differ. Circulatory adaptation to removal and reinfusion of 10% of the estimated blood volume was identical in salt-water and fresh-water-adapted ducks. It is concluded that even excessive chronic salt loading resulting in chronic hyperosmolality with high plasma levels of sodium and antidiuretic hormone does not alter hemodynamic adaptation, provided that efficient compensating mechanisms are at the animal's disposal.

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 (PAVP, 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 X 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 X 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.

Blood volume changes and arginine vasotocin (AVT) blood concentration in conscious fresh water and salt water adapted ducks.

Blood volume changes consisting in the removal and reinfusion respectively, of 10% of the estimated blood volume (23.2 ml on average) were induced to determine their effects on the blood concentration of arginine vasotocin (AVT), the antidiuretic hormone (ADH) of birds, in fresh water adapted ducks (water ducks) with blood osmolalities and ADH concentrations similar to those of normally hydrated mammals, and in salt water adapted ducks (salt ducks) with chronically elevated blood osmolalities and ADH concentrations. The investigations were carried out in steady state conditions, when infusion of 1 ml . min-1 of isotonic saline was matched by the excretion in water ducks and when infusion of 0.4 ml . min-1 of 1,000 mosmolal saline was matched by the salt gland excretion in the salt ducks. After blood removal, AVT blood concentration (mean +/- SE) increased from 6.5 +/- 0.4 to 8.4 +/- 0.6 pg . ml-1 in water ducks and from 18.1 +/- 1.6 to 22.6 +/- 1.9 pg . ml-1 in salt ducks. The respective blood osmolalities of 297.4 +/- 1.4 and 318.6 +/- 3.3 mOsm . kg-1 did not change. Reinfusion of the blood after steady-state conditions had been reattained decreased blood AVT from 7.9 +/- 0.7 to 6.7 +/- 0.5 pg . ml-1 in water ducks. In the salt ducks AVT concentration had already returned to the control level before blood reinfusion which induced no further reduction. The blood osmolalities remained unchanged in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Control of central release of vasopressin.

A diffuse extrahypophyseal vasopressinergic system has been described in the brain, and vasopressin (AVP) has also been identified in the cerebrospinal fluid (CSF) of several species. Administration of AVP to the central nervous system has been found to influence several brain functions. It has been suggested therefore that this peptide may act as a physiologically significant neuromodulator of the central nervous system functions, including the control of the body fluid homeostasis. However, the mechanisms controlling the central release of AVP are poorly recognized. The purpose of the present investigation was to find out whether the release of AVP into the CSF is controlled by volume and osmotic stimuli and whether it may be relevant to the control of water intake. The experiments were performed on conscious dogs chronically implanted with a device enabling the withdrawal of CSF from the anterior part of the third ventricle which is situated in the vicinity of abundant vasopressinergic fibers. AVP measured by radio-immunoassay and osmolality were determined in blood and CSF samples taken simultaneously. 24 h dehydration caused a significant elevation of plasma (Posm) and CSF (CSFosm) osmolalities as well as of plasma (PAVP) and of CSF (CSFAVP) AVP concentrations. During rehydration total water intake (TWI) X kg-1 b.w. was significantly correlated with Posm and PAVP as well as with CSFosm and CSFAVP prior to drinking. Rehydration caused Posm, PAVP, CSFosm and CSFAVP to decrease significantly within 90 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasopressin in blood and third ventricle CSF of dogs in chronic experiments.

A device for chronic implantation was developed that allowed sampling of cerebrospinal fluid (CSF) from the anterior part of the third cerebral ventricle (A3V) of dogs in repeated experiments for up to 4 mo. Osmolalities, electrolyte concentrations, and concentrations of arginine vasopressin (AVP) measured with a radioimmunoassay were determined in repeated experiments on the chronically prepared animals under conditions of normal hydration, both in the conscious state and during inhalation anesthesia. In conscious dogs, AVP concentrations in plasma and CSF were 3.3 +/- 0.4 and 21.8 +/- 2.5 pg X ml-1, respectively. During anesthesia without surgical interference, the AVP concentrations in plasma and CSF were increased twofold above the levels obtained in conscious dogs. During the time of observation (180 min) all measured parameters remained constant. The AVP concentrations in plasma and CSF samples collected during the surgical procedure of device implantation were about 10-fold higher than in the samples collected during the conscious state. Thus, in each experimental condition, AVP concentration in the CSF collected from the A3V was consistently higher than that in the simultaneously collected blood samples.