Hepatic Osmoreceptors Research Articles

Time course of synergistic interaction between DOCA and salt on blood pressure: roles of vasopressin and hepatic osmoreceptors

In DOCA-salt rats, the time course of the synergistic interaction between osmolality and DOCA to produce hypertension is unknown. Therefore, in rats 2 wk after implantation of subcutaneous silicone pellets containing DOCA (65 mg) or no drug (sham), we determined blood pressure (BP) and heart rate (HR) responses, using telemetric pressure transducers, during 2 wk of excess salt ingestion (1% NaCl in drinking water). BP was unaltered in sham rats after increased salt, but in DOCA rats BP increased within 4 h. The initial hypertension of 30-35 mmHg stabilized within 2 days, followed approximately 5 days later by a further increment of approximately 30 mmHg. HR first decreased during the dark phase; the second phase was linked to an abrupt increase in HR and BP variability and decreased HR variability. Pressor responses to acute intravenous hypertonic saline infusion were doubled in DOCA-treated rats via vasopressin and nonvasopressin mechanisms. Only in DOCA-treated rats, portal vein hypertonic saline infusion increased BP, which was prevented by V(1) vasopressin blockade. After 2 wk of DOCA-salt, oral ingestion of water rapidly decreased BP. Intraportal infusion of water did not lower BP in DOCA-salt rats, suggesting that hepatic osmoreceptors were not involved. In summary, the hypertension of DOCA-treated rats consuming excess salt exhibits multiple phases and can be rapidly reversed. Hypertonicity-induced vasopressin and nonvasopressin pressor mechanisms that are augmented by DOCA, and hepatic osmoreceptors may contribute to the initial developmental phase. With time, combined DOCA-salt induces marked changes in the regulation of the autonomic nervous system, which may favor hypertension development.

Hepatic denervation does not affect plasma vasopressin response to intragastric hypertonic saline in conscious rats.

Peripheral osmoreceptors monitor dietary NaCl and modify central nervous system and renal sympathetic nervous system activity accordingly. Experimental evidence suggests that these responses are dependent on the hepatic nerves. Peripheral osmoreceptors also modify arginine vasopressin (AVP) secretion. However, although hepatic denervation reportedly blunts activation of both supraoptic and paraventricular hypothalamic neurons after intraportal NaCl infusion, the role of the hepatic nerves in the AVP release has not been directly examined. The present study tests the hypothesis that the hepatic nerves modify AVP release in response to intragastric NaCl infusion. Wistar-Kyoto rats (WKY) received either hepatic denervation or a sham operation. Intragastric NaCl infusion significantly elevated plasma AVP in both sham-operated WKY and hepatic-denervated WKY, and the responses were not different between these groups. Second, previous studies suggest that both AVP secretion and baroreflexes are blunted in spontaneously hypertensive rats (SHR), deficits that contribute to the observed hypertension in SHR. We hypothesized that SHR also have a blunted peripheral osmoreceptor reflex and that this contributes to NaCl-sensitive hypertension. In contrast to our prediction, in SHR intragastric NaCl infusion induced an increase in plasma AVP that was similar to that in the WKY groups. Thus, although hepatic osmoreceptors are important for chronic regulation of arterial pressure, renal sympathetic nervous system activity, and the activity of hypothalamic neurons, they do not appear to influence plasma AVP concentration in response to intragastric NaCl.

Plasma arginine vasopressin response to oral, gastric, and intravenous water load in patients with cirrhosis

Background/Aims: Hepatic osmoreceptors are sensitive to changes in portal blood osmolity and cause variations in plasma antidiuretic hormone and water diuresis, which prevent major systemic osmotic changes. Insensitivity of hepatic osmoreceptors might contribute to maintaining increased plasma levels of antidiuretic hormone and negative free water clearance after oral hydration in some cirrhotic patients. Methods: We measured free water clearance and plasma arginine vasopressin levels in basal conditions and after oral, intravenous, and intragastric water overload in control subjects (group I) and patients with cirrhosis (some with a positive [group II] and some a negative [group III] free water clearance). Results: In groups I and II, no significant differences in plasma arginine vasopressin levels were found regardless of the route used for hydration. In group III, plasma levels were significantly higher between 0 and 75 minutes after intragastric hydration than after oral or intravenous hydration. No significant changes in plasma osmolality were detected between minute 0 and 20 after the end of oral or intragastric hydration, although plasma arginine vasopressin decreased significantly only 5 minutes after the oral hydration. Group III patients showed evidence of autonomic neuropathy. However, this dysfunction was unrelated to the insensitivity to gastric hydration. Conclusions: Hepatic osmoreceptors seem to be disturbed in some cirrhotic patients, although this dysfunction may be compensated for by normally functioning oropharyngeal and hypothalamic osmoreceptors.

Reflex control of renal nerve activity originating from the osmoreceptors in the hepato-portal region

The reflex effects of hepatic osmoreceptors on the renal sympathetic nerve activity (RNA) were studied in 30 pentobarbital anesthetized, vagotomized and sino-aortic baroreceptor denervated (SAD + VD) rabbits. The changes in mean arterial pressure (MAP), heart rate (HR), and RNA were examined when 9% NaCl, 6.5% LiCl or 50% glucose solution was infused into the hepatic portal vein at a rate of 0.15 ml/kg/min for 10 min. Infusion of 9% NaCl solution into the hepatic portal vein increased the plasma osmolality by 10.8 ± 1.0 mOsmol/kg from the control level in the blood of the hepatic portal vein and by 2.8 ± 2.0 mOsmol/kg from the control level in the systemic blood. MAP was significantly elevated by 10.2 ± 5.0 mmHg but HR did not change with hepatic portal infusion of 9% NaCl solution. Intraportal infusion of 9% NaCl solution significantly decreased the RNA by 28.6–34.2% from the control level, 6.5% LiCl solution by 28.6 ± 4.7%, and 50% glucose solution by 26.2 ± 3.0%. Femoral arterial infusion of hypertonic NaCl solution, however, did not evoke any significant change in RNA in SAD + VD rabbits. These findings suggest that increases in osmolality and NaCl concentration in the systemic circulation do not result in a decrease of RNA. Furthermore, after section of the anterior and posterior plexus of the hepatic nerve, hepatic portal infusion of hypertonic NaCl solution elicited no change in RNA. The present data indicate that an increase in osmolality in the hepatic portal venous blood results in a reflex decrease of RNA. This reflex may be important for restoration of a postprandial increase in osmolality.

The effects of streptozotocin-induced diabetes in rats on ingestion patterns of water, sucrose and sodium saccharin

S 239 The Effects of Streptozotocin-induced Diabetes in Rats on Ingestion Patterns of Water, Sucrose and Sodium Saccharin. JAMES C. SMITH. Department of Psychology, Florida State University, Tallahassee, FL 32306, U.S.A. Male Sprague-Dawley rats were given a single i.p. streptozotocin injection (SZ) to induce diabetes. Rats with blood glucose levels below 300 mg/dl were eliminated from the study. The rats were tested in special cages where all licks on either of two drinking tubes and entries into a food chamber were recorded as breaks in IR beams. Ingestion activity was recorded every 6 set over daily 23 h periods. Both food and water intake by the SZ rats increased. Pattern analysis revealed that these increases were due to a marked increase in daytime ingestion and by a significant increase in ingestion bout length. The patterns of ingestion of sucrose and sodium saccharin are also presented. Hepatic Osmoreceptors and Water Intake. J. SOBOCkKA. Department of Clinical and Applied Physiology, School of Medicine, Warsaw, Poland. The purpose of this study was to find out whether changes of blood osmolality in hepatic portal circulation influence water intake (WI). Eight dogs were chronically implanted with a catheter introduced into the hepatic portal vein. The dogs were made thirsty by i.v. 5% NaCl infusion. WI during and 60min after intraportal (i.p.) 0.45%, 0.9% and 1.8% NaCl infusions as well as plasma osmolality were measured. The results were compared to those obtained during infusion of the same solutions systemically. WI during i.v. infusion of0.45% and 1.8% NaCl were 156.7 k43.4ml and 167.5 k44.8 ml, respectively. 1.~. infusion of 045% NaCl decreased WI to 65.6 k 145 ml whereas i.p. 1.8% NaCl increased WI to 206.9 k42.6 ml in spite of lack of differences in systemic plasma osmolality. The data support the role of hepatic portal osmoreceptors in control of water intake. Secular Trends in Development of Obesity in Childhood. THORKILD I. A. SBRENSEN and THOMAS BAYER. Psykologisk Institut, Kommunehospitalet and Biostatistical Research Unit, University of Copenhagen, Copenhagen, Denmark. On the basis of school health record data from a sub-sample of obese draftees and a random sample, we generated logistic regression models predicting development of obesity at draftee age from longitutinal body mass index (BMI) data in childhood. It was possible to predict the rise in prevalence of adult obesity by applying the models incorporating BMI at ages 7 through 13 years to data of the seven birth cohorts (1931,1941,1944, 1947, 1953). This indicates that the cause of the steep rise in prevalence of adult obesity is from environmental exposure before and during school ages increasingly affecting the children born after 1941. The Hypothalamus Affects Sympathetic Activity During Exercise, Dependent on the Nutritional State. A. B. STEFFENS and G. J. VAN DIJK. Department of Animal Physiology, University of Groningen, Haren, The Netherlands. During exercise rats fed carbohydrate (CH) free food show larger increases in plasma norepinephrine (NE) and epinephrine (E) levels than rats fed CH-rich food. After exercise, plasma E declines to basal levels again in both conditions. NE declines only slightly so that the level remains high in CH-free fed rats. The exaggerated sympathetic response in CH-free fed animals is probably mediated by the hypothalamus in response to a change in metabolic feedback in those rats. This serves the release of sufficient glucose and free fatty acids to cover the metabolic needs.

Hepatic osmoreceptors and water intake

Hepatic osmoreceptors and water intake

An hepatic osmoreceptor mechanism in the rat: electrophysiological and behavioral studies.

Rat liver was perfused with Ringer solution through the portal vein by use of a perfusion system which was designed to switch from standard Ringer solution to hypertonic or hypotonic Ringer solution. Neural responses to the osmotic change in the perfusion solutions were analyzed. They showed that two different types of osmosensitive afferent fibers exist in the hepatic vagus; one is characterized by increasing the frequency of spike discharges responding to higher osmotic pressure, while the other shows the same response to lower osmotic pressure. Behavioral changes caused by hepatic vagotomy were also observed. Though no differences could be detected in routine behavior (e.g., daily intakes of food and water, body-weight increase) between the vagotomized and the sham-operated rats, the former lost the ability to adjust urine concentration immediately in response to osmotic changes in the internal environment. These results provide evidence for the hypothesis that hepatic osmoreceptors exist in the rat.

Hepatic osmoreceptors?

1. The effects of 0.45% saline infusions into the portal vein of conscious and anaesthetized dogs have been compared with similar infusions through a systemic vein.2. Measurements were made of plasma and urinary osmolality, sodium, potassium and chloride concentrations and urine flows; osmolal clearances, free water clearances, the percentage of the infused loads excreted at given times, and rates of sodium and potassium excretion in the urine, were calculated.3. In the conscious and anaesthetized series of experiments no significant differences were found between the portal and systemic routes of infusion.4. For both the portal and systemic routes of infusion there was a significantly smaller diuretic response to the saline infusion in anaesthetized as compared with conscious animals.5. These results do not support the concept of hepatic osmoreceptors occurring in the dog.

Elimination of the hepatic branches of the vagal nerve in conscious rats and its influence on the hepatogenous diuresis--indirect evidence for the afferent vagal ppathway of the hepatic osmoreceptors

Elimination of the hepatic branches of the vagal nerve in conscious rats and its influence on the hepatogenous diuresis--indirect evidence for the afferent vagal ppathway of the hepatic osmoreceptors