vasopressin--1-(1-mercaptocyclohexaneacetic-acid)-2-(o--methyl-l-tyrosine)-8-l-arginine- and Diabetes-Insipidus

To elucidate the role of arginine vasopressin (AVP) in the development of stress-induced gastric ulcer, the mucosal lesions after restraint and water immersion were examined in Brattleboro strain rats with hereditary hypothalamic diabetes insipidus (DI) and in Long-Evans rats (LE) used as controls. Restrained animals were immersed in water for 2 h, and the size of lesion was expressed as percentage of the lesion area to the total glandular mucosal area, which were defined as ulcer index (UI). In DI rats, UI was significantly higher than in control LE rats, despite the attenuated responses of plasma adrenocorticotropic hormone (ACTH) to stress. Although subcutaneous injection of selective antidiuretic analogue 1-desamino-8-D-AVP did not affect UI, intracerebroventricular (icv) administration of AVP reduced UI in DI rats, and icv administration of V1 antagonist [d(CH2)5Tyr(Me)]AVP elevated UI in LE rats. These results indicate that endogenous AVP plays a role in preventing the formation of gastric ulcers induced by stress via a central V1 receptor. Furthermore, we suggest that elevation of ACTH in plasma is not essential in the development of stress-induced gastric ulcer in rats.

Topics: Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Cerebral Ventricles; Deamino Arginine Vasopressin; Diabetes Insipidus; Epinephrine; Gastric Mucosa; Immersion; Injections, Intraventricular; Injections, Subcutaneous; Male; Norepinephrine; Rats; Rats, Brattleboro; Restraint, Physical; Species Specificity; Stomach Ulcer; Stress, Psychological

The role of vasopressin in the development of gastric hemorrhagic erosions induced by the oral administration of 1 mL of 75% ethanol in rats was studied. The area of the lesions in homozygous Brattleboro rats, having a defective vasopressin synthesis, was only 20% of that found in Wistar and heterozygous Brattleboro rats, which have normal vasopressin production. It is well known that vasopressin acts via the V1 (pressor) and V2 (antidiuretic) receptors. Administration of V1 and V2 vasopressin-receptor agonists and antagonists in this model showed that pressor-receptor activity is needed for the generation of all lesions in Wistar and heterozygous Brattleboro rats. Ethanol damage to the gastric mucosa was diminished by the V1 antagonist with similar efficacy as in the case of a vasopressin deficiency. Administration of the V1 antagonist and the absence of endogenous vasopressin were shown to protect the deeper layer of the gastric mucosa (assessed by histology) and to reduce significantly the ethanol-induced vascular injury and increase in vascular permeability (assessed by the monastral blue technique). Thus, endogenous vasopressin is clearly of great importance in the pathogenesis of gastric hemorrhagic lesions induced by ethanol. These results strongly suggest that vasopressin is an endogenous aggressor toward the gastric mucosa.

Topics: Animals; Arginine Vasopressin; Diabetes Insipidus; Ethanol; Female; Gastric Acid; Gastric Emptying; Gastric Mucosa; Hydrogen-Ion Concentration; Peptic Ulcer Hemorrhage; Rats; Rats, Brattleboro; Rats, Inbred Strains; Stomach; Vasopressins

Cysteamine (beta-mercaptoethylamine, CSH) has been reported to have various effects on the neuroendocrine system. Reports indicate CSH decreases pituitary oxytocin (OT) without affecting pituitary vasopressin (VP). However, preliminary studies from our laboratory strongly indicate that CSH has an effect on VP release. Experiments were conducted with dibenzyline-treated, urethane-anesthetized, male Sprague-Dawley (SD) rats. Rats were injected with 4 mU of standard VP and 4 mg/100 g of CSH. Administration of VP resulted in an increase in mean arterial pressure (MAP) of 23.5 +/- 3.2 mm Hg. Administration of CSH resulted in a consistent, immediate decrease in MAP of 13.0 +/- 2.0 mm Hg prior to an increase of 21.0 +/- 2.6 mm Hg. The effects due to VP and CSH were strikingly different; the CSH-induced MAP rise took longer to peak and to return to baseline. Both the VP- and CSH-induced MAP rise were markedly inhibited by a prior administration of a specific VP antagonist d(CH2)5[Tyr(Me)]AVP. In addition, the typical increase in MAP observed in SD rats following CSH administration was substantially reduced when the same dose was administered in homozygous diabetes insipidus (HODI) rats. The data presented here strongly suggest that CSH-induced MAP elevation is due to the release of VP from the pituitary gland.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Cysteamine; Diabetes Insipidus; Male; Rats; Rats, Inbred Strains; Vasopressins

The cardiovascular effects of an acute haemorrhage (2% of the body weight) were studied over a 60 min period in three groups of rats: (a) Brattleboro rats with hereditary hypothalamic diabetes insipidus (b.d.i.) lacking circulating vasopressin, (b) control rats of the parent Long Evans (l.e.) strain, and (c) l.e. rats treated with an antagonist of the vascular action of vasopressin. Prior to the haemorrhage there were no significant differences between the three groups of rats with respect to mean arterial blood pressure, cardiac output, stroke volume or total peripheral resistance. Following the haemorrhage cardiac output and stroke volume were severely reduced in all three groups of rats. Total peripheral resistance was relatively unaffected in antagonist-treated l.e. rats and b.d.i. rats, but rose substantially in response to the loss of blood in the control l.e. group. Both total peripheral resistance and mean arterial blood pressure were markedly greater in the untreated l.e. control rats than in the other two groups of animals during the first 20 min after haemorrhage. The mean heart rate measured in Brattleboro rats was elevated compared with that of control l.e. rats throughout the experiment and, in addition, significantly greater than that of antagonist-treated l.e. rats during the first 40 min after the haemorrhage. Survival rate for the b.d.i. rats following the 2% haemorrhage was lower than that for l.e. control rats and antagonist-treated l.e. rats. The results indicate that the recovery of the blood pressure following an acute arterial haemorrhage is significantly influenced by vasopressin, particularly during the first 20 min, and that the predominant effect of the hormone is to increase the total peripheral resistance. The higher mortality associated with volume depletion in the b.d.i. rats is unlikely to be directly related to the absence of the vascular action of vasopressin, since administration of the vasopressin antagonist to normal l.e. rats does not reduce their survival rate.

Topics: Anesthesia, General; Animals; Arginine Vasopressin; Blood Pressure; Diabetes Insipidus; Hemodynamics; Hemorrhage; Male; Rats; Rats, Brattleboro; Time Factors