Biomedical subjects

M D Drutarosky

Publications and source records attributed to M D Drutarosky.

5 recordsLinked to original sources

PubMed1991

Brain oxytocin receptors mediate corticotropin-releasing hormone-induced anorexia.

Central administration of corticotropin-releasing hormone (CRH) is known to inhibit food intake and stimulate pituitary oxytocin (OT) secretion in rats. These experiments addressed the possibility that the inhibition of food intake that follows central CRH administration is mediated through oxytocinergic pathways. Male food-deprived rats, with stable baseline food intakes after intracerebroventricular (icv) injections of artificial cerebrospinal fluid, received 150 pmol of CRH icv. Food intake was inhibited by 62 +/- 5% during a 90-min test period. Pretreatment with 9 nmol of the OT antagonist [d(CH2)5, Tyr(Me)2, Orn8]vasotocin icv completely eliminated the inhibition of food intake produced by icv CRH. In contrast, pretreatment with the OT-receptor antagonist did not significantly alter pituitary secretion of adrenocorticotropic hormone and OT stimulated by icv CRH. The results of these experiments implicate OT as a possible central mediator of CRH-induced anorexias in rats, particularly those that are accompanied by stimulation of neurohypophysial OT secretion.

Adrenocorticotropic Hormone↗

PubMed1991

Brain oxytocin receptor antagonism blunts the effects of anorexigenic treatments in rats: evidence for central oxytocin inhibition of food intake.

The inhibition of food intake in rats that results from various anorexigenic treatments is frequently associated with pituitary secretion of oxytocin (OT), but is not caused by circulating OT. We, therefore, evaluated the potential role of brain OT in mediating anorexia induced in rats by systemic administration of cholecystokinin (CCK), hypertonic saline (HS), or lithium chloride (LiCl), treatments that are known to stimulate pituitary OT secretion as well as to inhibit food intake. Food intake was analyzed in 22-h food-deprived rats pretreated with icv injections of either artificial cerebrospinal fluid (aCSF) or 9 nmol of an OT receptor antagonist, [d(CH2)5, Tyr(OMe)2,Orn8]vasotocin (OVT), which was the dose found to be most effective to antagonize the anorexia induced by CCK and HS. Pretreatment with the OT receptor antagonist icv significantly blunted the anorexigenic effect of each agent. After CCK (10 micrograms/kg, ip), food intake increased from 28 +/- 5% of basal intake after a CSF icv to 48 +/- 8% after OVT icv (P less than 0.01); after HS (2 ml 2 M NaCl, ip), food intake increased from 9 +/- 4% of basal intake after aCSF icv to 43 +/- 7% after OVT icv (P less than 0.01); and after LiCl (1.125 mmol/kg, ip), food intake increased from 55 +/- 4% of basal intake after a CSF icv to 80 +/- 9% after OVT icv (P less than 0.01). These data support the hypothesis that pituitary secretion of OT after anorexigenic treatments in rats is associated with coactivation of centrally projecting brain OT pathways, some of which are causally related to the induced inhibition of food intake.

Angiotensin Receptor Antagonists↗

PubMed1989

Adaptive responses to sustained volume expansion in hyponatraemic rats.

Studies were carried out to evaluate adaptive responses to water retention in an experimental model of the syndrome of inappropriate antidiuresis (SIAD). Hyponatraemia was induced by continuous s.c. infusions of the antidiuretic vasopressin analogue 1-deamino-[8-D-arginine]-vasopressin in rats ingesting a 5% (w/v) dextrose solution. After 48 h of sustained decreases in the plasma concentration of Na+ to 23-25% of normal levels, all body fluid compartments were significantly expanded: plasma volume estimated by changes in plasma protein concentration was increased by 26%, extracellular fluid volume estimated by 22Na volume of distribution was increased by 24%, and total body water estimated by 3H2O volume of distribution was increased by 16%. Despite marked increases in all body fluid compartment volumes, mean arterial blood pressure was only modestly increased to 110 +/- 2 mmHg in conscious hyponatraemic rats. Consistent with the sustained volume expansion, both basal and stimulated plasma renin activities were significantly suppressed in the hyponatraemic rats. Plasma vasopressin levels were similarly suppressed, and the hyponatraemic rats showed a striking absence of endogenous vasopressin secretion in response to marked intravascular volume depletion (15-45%) produced by s.c. administration of polyethylene glycol. Plasma concentrations of atrial natriuretic peptide were initially stimulated four- to fivefold above basal levels in response to the water-induced volume expansion, but by 48 h fell to ranges not significantly different from basal unstimulated levels, despite continued plasma and extracellular fluid volume expansion at that time. These results illustrate that multiple haemodynamic and hormonal adaptive responses occur with sustained dilutional hyponatraemia in rats, and suggests that these can be of sufficient magnitude to allow continued water retention without necessarily provoking either escape from antidiuresis or continued natriuresis. In contrast with previous studies in experimental animals in which hyponatraemia was maintained by continuous forced administration of hypotonic fluid, rats in this model reached a steady state with characteristics resembling many of those observed clinically in patients with SIAD.

Animals↗

PubMed1988

Adaptation to chronic hypoosmolality in rats.

A method for maintaining chronic severe hypoosmolality in rats is described utilizing subcutaneous infusions of the antidiuretic vasopressin analogue 1-deamino-[8-D-arginine] vasopressin (DDAVP) at rates of 1 or 5 ng/hr via osmotic minipumps in combination with self-ingestion of a concentrated, nutritionally-balanced liquid diet. Using these methods, 97.3% of all rats studied achieved stable levels of severe hyponatremia (plasma [Na+] = 111.6 +/- 0.5 mEq/liter, N = 213), which was sustained for periods of time ranging from two to five weeks. Mortality was low (1.8%) and observable morbidity was not noted over a series of studies encompassing 4,628 rat days of sustained hypoosmolality. Analysis of food intake and body weight revealed no evidence of tissue catabolism at any time with the lower (1 ng/hr) DDAVP infusion rate, and only during the first week with the higher (5 ng/hr) rate. Metabolic balance studies during 13 days of sustained hypoosmolality demonstrated the dilutional nature of the hypoosmolality, and only a limited degree of renal escape from the antidiuretic effects of DDAVP (urine osmolalities 800 to 1200 mOsm/kg H2O). Studies of brain water and electrolyte contents demonstrated complete normalization of brain volume after 14 to 28 days of sustained hypoosmolality, the major part of which (70%) could be accounted for by loss of brain electrolytes. Both natriuresis and kaliuresis occurred during the first five days of hypoosmolality, and were of sufficient magnitude to suggest some degree of adaptation of other body fluid compartments via electrolyte losses as well. These results indicate that rats have substantial capacity to tolerate prolonged severe hypoosmolality with little morbidity and mortality as long as proper attention is paid to their nutritional requirements, and provide further evidence that brain volume regulation likely represents the major adaptive mechanism that allows survival despite sustained hypoosmolality.

Adaptation, Physiological↗

PubMedDate not supplied

Oxytocin and an oxytocin agonist administered centrally decrease food intake in rats.

Intracerebroventricular administration of oxytocin (OT) and an OT agonist significantly decreased food intake in a dose-related manner in fasted rats. Central administration of an OT antagonist by itself (up to doses of 8 nmol) did not potentiate deprivation-induced food intake, but pretreatment with the OT receptor antagonist prevented the expected inhibition of food intake produced by OT and the OT agonist. Once-daily ICV injections of OT led to the development of tolerance to the inhibitory effects on food intake by the third day of treatment, but daily pretreatment with the OT antagonist prevented the development of this tolerance. In addition to causing decreased food intake, ICV administration of OT significantly increased grooming behavior but produced no dyskinesias. The inhibitory effect of OT on food intake was characterized by decreased amounts of food intake but a normal pattern of ingestion. The anorexia produced was central in nature and was not associated with altered plasma levels of hormones involved in caloric homeostasis or with changes in blood glucose. The OT agonist had relatively little effect on water intake when given in doses that significantly inhibited food intake. These results support the hypothesis that specific OT receptors within the central nervous system participate in the inhibition of feeding under certain conditions in rats.

Angiotensin Receptor Antagonists↗