Character of Auerbach's plexus receptors in the stomach and small intestine]

The motility of the stomach and jejunum in 8 fed dogs with the intact vagus nerves was registered by the balloon method. Subcutaneous injection of benzohexonium (0.125--0.5 ml of 2.5% soltuion) and atropine (0.12--0.25 ml of 0.1% solution) or metacine (0.125--0.25 ml of 0.1% solution) to 6 dogs proved to induce a transition from digestive motility to the periodic form after a transient depression of the digestive motility. The same effect followed injection of 0.5--1.0 ml of 0.1% atropine only in 2 dogs and 1.0 ml of 0.1% metacine in 1 dog. Since retention of periodic motility following food consumption was inherent for vagotomized dogs, a conclusion was drawn that the experimental dog had "pharmacologic vagotomy". It was suggested that the muscarine receptors on the Auerbach's plexus cells exceeded the nicotine receptor in number.     

Octreotide-induced drinking, vasopressin, and pressure responses: role of central angiotensin and ACh

The involvement of central angiotensinergic and cholinergic mechanisms in the effects of the intracerebroventricularly injected somatostatin analog octreotide (Oct) on drinking, blood pressure, and vasopressin secretion in the rat was investigated. Intracerebroventricular Oct elicited prompt drinking lasting for 10 min. Water consumption depended on the dose of Oct (0.01, 0.1, and 0. 4 microgram). The drinking response to Oct was inhibited by pretreatments with the intracerebroventricularly injected angiotensin-converting enzyme inhibitor captopril, the AT(1)/AT(2) angiotensin receptor antagonist saralasin, the selective AT(1) receptor antagonist losartan, or the muscarinic cholinergic receptor antagonist atropine. The dipsogenic effect of Oct was not altered by prior subcutaneous injection of naloxone. Oct stimulated vasopressin secretion and enhanced blood pressure. These responses were also blocked by pretreatments with captopril or atropine. Previous reports indicate that the central angiotensinergic and cholinergic mechanisms stimulate drinking and vasopressin secretion independently. We suggest that somatostatin acting on sst2 or sst5 receptors modulates central angiotensinergic and cholinergic mechanisms involved in the regulation of fluid balance.     

Effect of vasopressin and its analogs on blood coagulation in rats

A change in the response of the blood coagulation system to the intravenous injection of vasopressin (AVP), DDAVP and DGAVP has been studied in the experiments on white rats. Intensification of the procoagulant activity on AVP is of the dose-dependent character. Maximal effect is observed 5-15 min after i.v. injection of AVP in a dose of 4 mg/kg. The administration of this peptide increases the fibrinolytic activity, that is connected with an increase in the level of plasminogen activator. DDAVP and DGAVP have a weaker effect on fibrinolysis. AVP and DDAVP increase the level of FVIII by 5-6% during the first minutes, but DGAVP increases the level of FVIII only after 15-30 minutes. While using AVP, DDAVP and DGAVP in clinical practice it is necessary to allow for their hormonal action, the initial state of haemostasis and the age of patients.     

A central link between angiotensinergic and cholinergic systems; role of vasopressin

Participation of central cholinergic system in the effects of intracerebroventricular (i.c.v.) injection of angiotensin II (Ang II) on blood pressure and heart rate was studied in conscious, freely moving rats. Ang II dose-dependently increased blood pressure and decreased heart rate. Both atropine and mecamylamine (i.c.v.) pretreatments prevented the cardiovascular effects of Ang II. Pretreatment with a vasopressin V1 antagonist also prevented the cardiovascular responses to Ang II. Our data suggest that the central pressor effect of Ang II is mediated in part by central acetylcholine via both muscarinic and nicotinic receptors, and vasopressin participates in this effect through V1 receptors.     

Bivalirudin in combination with heparin to control mesenchymal cell procoagulant activity

Islet and hepatocyte transplantation are associated with tissue factor-dependent activation of coagulation which elicits instant blood mediated inflammatory reaction, thereby contributing to a low rate of engraftment. The aim of this study was i) to evaluate the procoagulant activity of human adult liver-derived mesenchymal progenitor cells (hALPCs), ii) to compare it to other mesenchymal cells of extra-hepatic (bone marrow mesenchymal stem cells and skin fibroblasts) or liver origin (liver myofibroblasts), and iii) to determine the ways this activity could be modulated. Using a whole blood coagulation test (thromboelastometry), we demonstrated that all analyzed cell types exhibit procoagulant activity. The hALPCs pronounced procoagulant activity was associated with an increased tissue factor and a decreased tissue factor pathway inhibitor expression as compared with hepatocytes. At therapeutic doses, the procoagulant effect of hALPCs was inhibited by neither antithrombin activators nor direct factor Xa inhibitor or direct thrombin inhibitors individually. However, concomitant administration of an antithrombin activator or direct factor Xa inhibitor and direct thrombin inhibitor proved to be a particularly effective combination for controlling the procoagulant effects of hALPCs both in vitro and in vivo. The results suggest that this dual antithrombotic therapy should also improve the efficacy of cell transplantation in humans.     

Intracerebroventricular injection of hemicholinium-3 lowers blood pressure in conscious spontaneously hypertensive rats but not in normotensive rats

Intracerebroventricular (icv) injection of hemicholinium-3 (HC-3) in doses of 10–20 μg causes a dose-related decrease in the blood pressure of conscious spontaneous hypertensive (SH) rats but not of normotensive rats. HC-3 also reduces heart rate (HR) in both SH and normotensive rats. The bradycardia was blocked by intravenous injection of methylatropine, implicating increased vagal activity as a cause of the response. The decrease in HR also was blocked by icv injection of atropine but not by icv injection of mecamylamine, suggesting that the bradycardia is mediated via central muscarinic receptors. In contrast, the fall in blood pressure in SH rats was not influenced by intravenous administration of methylatropine or by the icv injection of either atropine or mecamylamine.     

Increase in vasopressin concentration and cardiodepressant activity in the blood dialysates after NMDA and hypertonic saline administration.

It has been demonstrated that electric stimulation of the central ends of cut vagus nerves or angiotensin II infusion cause an increase in vasopressin concentration and cardiodepressant activity in the sella turcica venous blood. The present study was an attempt to determine if the cardiodepressant factor and vasopressin were simultaneously released from the pituitary into the blood dialysate after osmotic stimulation, and whether excitatory amino acids are involved in this mechanism. The samples of dialysates of venous blood flowing from the sella turcica region and, for comparison, from the femoral vein were collected in anaesthetised rats. The concentration of vasopressin in blood dialysate was determined by radioimmunoassay, and cardiodepressant activity on spontaneously discharging pacemaker tissue of the right auricle of the right heart atrium. Osmotic stimulation or N-methyl-D-aspartic acid infusion caused an increase in cardiodepressant activity and vasopressin concentration in the blood dialysate from the sella turcica and from the femoral vein. A blockade of the excitatory amino acids receptors by specific and non-specific antagonists significantly inhibited the increase in the blood dialysate vasopressin concentration and cardiodepressant activity elicited by an intra-arterial injection of hypertonic saline. These data indicate that excitatory amino acids are involved in the mechanism of increase in blood vasopressin and cardiodepressant factor concentration in response to osmotic stimulation. These results also demonstrate the utility of blood minidialysis for simultaneous monitoring of active substances concentration in the blood.     

Comparison of Pasteur and Behringwerke antivenoms in envenoming by the carpet viper (Echis carinatus).

Bites and envenoming by the carpet viper Echis carinatus are common medical emergencies in parts of Nigeria, but the most effective use of the various commercially produced antivenoms in treatment has not been established. Pasteur Paris Echis monospecific and Behringwerke West and North Africa Bitis-Echis-Naja polyspecific antivenoms were compared in two groups of seven patients with incoagulable blood after E carinatus bites. In both groups spontaneous bleeding stopped within a few hours and local swelling subsided within two weeks after the initial antivenom injection. Pasteur antivenom (20-40 ml) restored blood coagulability within 12 hours in all cases, but 60--180 ml of Behringwerke antivenom was effective in only four cases. Persisting venom procoagulant activity was observed in the remaining three cases. Despite its potency in the mouse protection test, Behringwerke antivenom is unreliable and unpredictable in neutralising venom procoagulant in humans bitten by E carinatus.     

The neurohypophysial vasopressin content as influenced by modified cholinergic or adrenergic transmission during long-term dehydration in the white rat.

In rats dehydrated up to 12 days the neurohypophysial vasopressin content was determined by Dekański's method. Carbamylcholine inhibited somewhat the vasopressin depletion in the neurohypophysis, but not earlier than under severe dehydration (8th and 12th day). A single dose of atropine given 24 h prior to sacrifice to not dehydrated animals resulted in a diminution of the vasopressin content in the neurohypophysis; in animals dehydrated for four days and parallely atropinized the decrease of the neurohypophyseal vasopressin content was, on the contrary, considerably inhibited. Under severe dehydration, the treatment with atropine did not change the vasopressin stores in the neural lobe. Phenoxybenzamine inhibited the vasopressin depletion in the neural lobe following four days of dehydration. Under severe dehydration, amphetamine potentiated the effect of osmoreceptor stimulation. It is supposed that impulses of osmoreceptor origin are of some importance in determining the vasopressin release following changes of cholinergic or adrenergic transmission.     

Recombinant IFN-gamma synergizes with lipopolysaccharide to induce macrophage membrane procoagulants

Fibrin deposition is an important histopathologic feature of inflammation and is mediated, in part, by monocyte/macrophage procoagulants. rIFN gamma acted in synergy with suboptimal levels of bacterial LPS by priming thioglycollate-induced mouse peritoneal exudate cells (TG-PEC) to express high levels of surface procoagulant. TFN-alpha beta, TFN-alpha, IL-1, either alone or in combination with LPS or IFN-gamma, had no effect on macrophage procoagulant activity expression. In contrast to the dramatic increases of macrophage procoagulant activity induced by IFN-gamma/LPS, on exudate macrophages, normal peritoneal macrophages, or peripheral blood monocytes were unresponsive suggesting that the state of activation of the macrophage determines reactivity. IFN-gamma induced a Factor VIIa-like activity detected only after cell disruption. Synergy between LPS and IFN-gamma-induced procoagulants may occur as the result of the assembly of the thromboplastin (induced by LPS), Factor VII/VIIa complex on the macrophage surface. RNA synthesis was required for procoagulant induction. Procoagulant expression may, as for other cytokines involved in inflammatory responses, be regulated by short lived repressor proteins as low dose cycloheximide superinduced procoagulant responses to both LPS and IFN-gamma and caused the extracellular expression of procoagulant in response to IFN-gamma. This study suggests an important role for IFN-gamma in the assembly of components of the extrinsic coagulant cascade on the macrophage surface. The synergy between IFN-gamma and LPS may moderate macrophage-initiated fibrin deposition characteristic of inflammatory responses.     

Thyroid stimulating effect of exogenous vasopressin and oxytocin in hypophysectomized rats during immobilization stress

Male Wistar rats were hypophysectomized 1 week before restraint stress. The hypophysectomy caused a decrease of blood vasopressin (30%, P less than 0.05) and a diminution of the thyroid activity (the thyrocyte height lowered to 43%, P less than 0.01). The TSH concentration was about normal and remained constant during the experiment. After 20 min of the restraint stress, the vasopressin concentration reached 178% (P less than 0.01), but the thyroid did not response in rats with the intact hypophysis. In the hypophysectomized rats, the restraint stress caused neither essential changes of the blood vasopressin nor the thyroid function as compared with the hypophysectomized control. An injection of vasopressin (5.0 ng/100 g) or oxytocin (15.0 ng/100 g) resulted in a slight activation of the thyroid in the hypophysectomized rats but significantly stimulated in when combined with the restraint stress; vasopressin injection led to an increase of the thyrocyte height to 152% (P less than 0.01), oxytocin--to 126% (P less than 0.05). Thus, in hypophysectomized rats, vasopressin and oxytocin can influence the thyroid directly. Stressful conditions facilitate the thyroid stimulating effect of these nonapeptide neurohormones.     

Relation between the impairment of creatine kinase activity and lipid peroxidation in the membranes of heart mitochondria and sarcoplasmic reticulum in experimental ischemia

Experiments were conducted on rabbits under conditions of acute restriction of coronary blood flow (intravenous injection of vasopressin in a dose of 0.5 U/kg) and preliminary administration (1 h before vasopressin) of PP-256-Na antioxidant preparation. The activity of creatine kinase isoenzymes bound with sarcoplasmic reticulum and mitochondria membranes were studied as well as the content of diene conjugates in these membranes and accumulation of malonic dialdehyde. It is shown that an essential decrease in the enzyme activity in the membranes occurs against a background of a considerable increase in the content of diene conjugates and accumulation of malonic dialdehyde. A preliminary administration of the antioxidant produces a pronounced protective effect on the enzyme activity.     

Corticotropin releasing factor activity of CRF 41 in normal man is potentiated by angiotensin II and vasopressin but not by desmopressin

Multiple hypothalamic factors seem to influence ACTH release. In vitro and/or in vivo animal models have shown that angiotensin II, vasopressin and some of its analogs are ACTH secretagogues capable of potentiating the corticotropin releasing activity of CRF41. Since these effects are controversial in man, we investigated in 3 groups of volunteers the corticotropin releasing activity of a 2h-infusion of angiotensin II (7 ng/kg/min), vasopressin (1 ng/kg/min) and desmopressin (1 ng/kg/min) given alone or in combination with a bolus injection of 100 micrograms CRF41 by measuring plasma concentrations of ACTH, cortisol, dehydroepiandrosterone and delta 4-androstenedione. Given alone angiotensin II and desmopressin had no significant effect in contrast to vasopressin which increased significantly the ACTH and steroid levels. Angiotensin II and vasopressin were both able to potentiate the corticotropin releasing activity of CRF41, whereas desmopressin was unable to produce such a potentiation. These results suggest that in man vasopressin and angiotensin II may well regulate the responsiveness of the pituitary-adrenal axis in various physiological or pathophysiological situations.     

Cancer procoagulant as a marker in monitoring the therapy in cases of oesophageal, stomach and colorectal cancer

Cancer procoagulant activity in the blood serum of patients with oesophagal, gastric and colorectal cancer was evaluated before and after the tumour removal. Cancer procoagulant activity was significantly higher before the operation in comparison to the control group and was reduced after a total operative procedure, whereas it was kept on a high level after a non-radical procedure or in cases of metastases. Examination results point to the possibility of using the evaluation of cancer procoagulant activity in monitoring the course of treatment of patients with oesophagal, gastric and colorectal cancer.     

Changes of rat plasma total low molecular weight antioxidant level after tabun exposure and consequent treatment by acetylcholinesterase reactivators

These experiments were performed on a rat model. The rats were divided into eight groups and consequently exposed to either a saline solution (control), atropine or a combination of atropine and tabun. The reactivation efficacy of the oximes was estimated on the rats exposed to tabun, atropine and a reactivator of AChE. The oximes HI-6, obidoxime, trimedoxime, K203 and KR-22836 were used as representative compounds of commonly available and new AChE reactivators. Besides the positive effect of the administered reactivators on blood AChE activity, the sizable modulation of low molecular weight antioxidant (LMWA) levels was also determined. The LMWA levels in the the animals treated with the oxime reactivators were decreased in comparison with the animals treated by atropine alone. It was found that the levels of LMWA returned to the level found in the control animals when either trimedoxime, K203 or KR-22836 were administered. The principle of oxime reactivator function and a novel insight into AChE activity regulation and oxidative stress is discussed.     

Effects of parathormone on 45Ca2+ accumulation in neurosecretory cells and contents of vasopressin in blood after administration of parathyroidin in parathyroid gland insufficiency]

The functional state of hypothalamic-hypophyseal-neurosecretory complex was studied in parathyroidin injection and hypofunction of the parathyroid glands. In these conditions vasopressin levels in blood of the rats increased. The incubation of the hypothalamus with parathormone and 45Ca2+, as well as the injection of parathyroidin increased 45Ca2+ transfer to the neurosecretory cells and vasopressin release in the blood. Various mechanisms of similar influence of the parathormone and hypofunction of the parathyroid glands on a vasopressin level in blood are discussed.     

Stimulation of testicular ornithine decarboxylase activity by arginine vasopressin

Intratesticular injection with arginine vasopressin caused stimulation of ornithine decarboxylase activity in the testes of immature rats. The increase in ornithine decarboxylase activity in response to arginine vasopressin was dose and time dependent. Maximal stimulation of ornithine decarboxylase activity occurred at 2 h after injection with 0.1 micrograms of arginine vasopressin. It was observed that stimulation of ornithine decarboxylase activity occurred in seminiferous tubules and in Leydig cells of the testis in response to arginine vasopressin.     

Hereditary blood coagulation factor-VII deficiency in the beagle: immunological characterisation of the defect

In the plasma of beagles known to be homozygotes for hereditary blood coagulation factor-VII deficiency, antibody neutralization assays indicate only slightly greater quantities of factor-VII related antigen than are detected by conventional assays of procoagulant activity. Plasma of one dog was depleted of factor-VII procoagulant activity by exposure to an immobilized antibody; the low level of activity originally present was then verified by titration with normal plasma. The plasma defect results from an incomplete deletion of synthesis.     

Role of rennin-angiotensin system in cholinergic agonist carbachol-induced cardiovascular responses in ovine fetus

To investigate the mechanisms underlying the cholinergic agonist carbachol-induced cardiovascular responses, changes of renin-angiotensin system were examined in fetal hormonal systems. In the ovine fetal model under stressless condition, the cardiovascular function was recorded. Blood samples were collected before (during baseline period) and after the intravenous administration of carbachol. Simultaneously, the levels of angiotensin I (Ang I), angiotensin II (Ang II) and vasopressin in the fetal plasma were detected by immunoradiological method. Also, blood gas, plasma osmolality and electrolyte concentrations were analyzed in blood samples. Results showed that in chronically prepared ovine fetus, intravenous infusion of carbachol led to a significant decrease of heart rate (P < 0.05), and a transient decrease followed by an increase of blood pressure (P < 0.05) within 30 min. After the intravenous infusion of carbachol, blood concentrations of Ang I and Ang II in near-term ovine fetus were both significantly increased (P < 0.05); however, blood concentration of vasopressin, values of blood gas, electrolytes and plasma osmolality in near-term ovine fetus were not significantly changed (P > 0.05). Blood levels of Ang I and Ang II in the atropine (M receptor antagonist) + carbachol intravenous administration group was lower than those in the carbachol group without atropine administration (P < 0.05). In conclusion, this study indicates that the near-term changes of cardiovascular system induced by intravenous administration of carbachol in ovine fetus, such as blood pressure and heart rate, are associated with the changes of hormones of circulatory renin-angiotensin system.     

Differing effects of vasopressin on regional cerebral blood flow of dogs following intracisternal vs. intra-arterial administration

We investigated the differential effect of the intracisternal and intraarterial administration of vasopressin on the regional cerebral blood flow (rCBF) in the parietal cortex of dogs. Regional CBF, velocity and blood volume were assayed by laser flowmetry. The intracisternal injection of 1 nmol vasopressin significantly increased the rCBF and velocity, without affecting blood volume. However, the intravertebral arterial injection of 1 nmol vasopressin significantly decreased the rCBF and velocity. This discrepancy can be explained by a difference in the affected vasculature; large blood vessels in the subarachnoid space vs. whole cerebral vascular system. The intracisternal and intraarterial injection of the nitric oxide inhibitor N^G-monomethyl-L-arginine reduced the rCBF from the base line, and significantly suppressed the rCBF elevation induced by vasopressin. The effect of vasopressin may be considered as the summation of the increased flow from the dilated large vessels via the release of nitric oxide from the endothelium, and of the decreased flow from the contracted small vessels.