Portal Vasculature Research Articles

The Gut and Energy Balance: Visceral Allies in the Obesity Wars

In addition to digesting and assimilating nutrients, the intestine and associated visceral organs play a key sensing and signaling role in the physiology of energy homeostasis. The gut, the pancreatic islets of Langerhans, elements in the portal vasculature, and even visceral adipose tissue communicate with the controllers of energy balance in the brain by means of neural and endocrine pathways. Signals reflecting energy stores, recent nutritional state, and other parameters are integrated in the central nervous system, particularly in the hypothalamus, to coordinate energy intake and expenditure. Our understanding of regulatory neural circuits and the signaling molecules that influence them has progressed rapidly, particularly after the discovery of the adipocyte hormone leptin. These discoveries have led to exploration of novel routes for obesity control, some of which involve gut-derived pathways.

Liver transplantation for severe intrahepatic non-cirrhotic portal hypertension

Liver transplantation for severe intrahepatic non-cirrhotic portal hypertension

Effect of breed on anatomy of portosystemic shunts resulting from congenital diseases in dogs and cats: a review of 242 cases

To evaluate the effect of species and breed on the anatomy of portosystemic vascular anomalies in dogs and cats. Retrospective study of 233 dogs and nine cats presenting to the University Veterinary Centre, Sydney. Case records were evaluated for breed, sex, age, anatomical and histological diagnosis. Cases were included when a portosystemic vascular anomaly resulted from a congenital or developmental abnormality of the liver or portal venous system. Disease conditions included single congenital portosystemic shunt with patent portal vasculature (214 dogs, nine cats), portal vein aplasia (nine dogs), multiple acquired shunts resulting from portal vein hypoplasia (seven dogs), biliary atresia (one dog) and microvascular dysplasia (one dog). One Maltese had a single, congenital shunt and multiple acquired shunts resulting from hepatic cirrhosis. Breeds that were significantly over-represented included the Maltese, Silky Terrier, Australian Cattle Dog, Bichon Frise, Shih Tzu, Miniature Schnauzer, Border Collie, Jack Russell Terrier, Irish Wolfhound and Himalayan cat. Bichon Frise with shunts were significantly more likely to be female than male (12:2, P < 0.001). Two hundred and fourteen dogs (91.4%), and all cats, had shunts that were amenable to attenuation. Inoperable shunts occurred in 19 dogs (8.2%). Fifty six of 61 (92%) operable shunts in large breed dogs were intrahepatic, versus 10/153 (7%) in small breeds (P < 0.0001). Breeds that were not predisposed to portosystemic shunts were significantly more likely to have unusual or inoperable shunts than dogs from predisposed breeds (29% versus 7.6%, P < 0.0001). No significant relationship between breed and shunt type could be determined in cats. Breed has a significant influence on shunt anatomy in dogs. Animals presenting with signs of portosystemic shunting may suffer from a wide range of operable or inoperable conditions. Veterinarians should be aware that unusual or inoperable shunts are much more likely to occur in breeds that are not predisposed to congenital portosystemic shunts.

Vascular Endothelial Cells Promote Acute Plasticity in Ependymoglial Cells of the Neuroendocrine Brain

Glial and endothelial cells interact throughout the brain to define specific functional domains. Whether endothelial cells convey signals to glia in the mature brain is unknown but is amenable to examination in circumventricular organs. Here we report that purified endothelial cells of one of these organs, the median eminence of the hypothalamus, induce acute actin cytoskeleton remodeling in isolated ependymoglial cells and show that this plasticity is mediated by nitric oxide (NO), a diffusible factor. We found that both soluble guanylyl cyclase and cyclooxygenase products are involved in this endothelial-mediated control of ependymoglia cytoarchitecture. We also demonstrate by electron microscopy that activation of endogenous NO release in the median eminence induces rapid structural changes, allowing a direct access of neurosecretory axons containing gonadotropin-releasing hormone (GnRH) (the neuropeptide controlling reproductive function) to the portal vasculature. Local in vivo inhibition of NO synthesis disrupts reproductive cyclicity, a process that requires a pulsatile, coordinated delivery of GnRH into the hypothalamic-adenohypophyseal portal system. Our results identify a previously unknown function for endothelial cells in inducing neuroglial plasticity and raise the intriguing possibility that endothelial cells throughout the brain may use a similar signaling mechanism to regulate glial-neuronal interactions.

Prolactin-regulated tyrosine hydroxylase activity and messenger ribonucleic acid expression in mediobasal hypothalamic cultures: the differential role of specific protein kinases.

Prolactin secretion from the anterior pituitary is tightly regulated by feedback onto the hypothalamic neuroendocrine dopaminergic (NEDA) neurons. Prolactin stimulates these neurons to synthesize and secrete dopamine, which acts via the pituitary portal vasculature to inhibit prolactin secretion from the pituitary lactotrophs. Despite the physiological importance of this feedback, relatively little is known about the signaling mechanisms responsible for prolactin activation of NEDA neurons. This issue has been examined here using a cell culture preparation of the fetal rat mediobasal hypothalamus. Prolactin stimulated a time- and concentration-dependent increase in catecholamine synthesis, which was maximal after 60-120 min (1 microg/ml prolactin) and inhibited by the prolactin antagonist Delta1-9-G129R-hPRL. This prolactin response was accompanied by a rise in the site-specific (ser-19, -31, and -40) phosphorylation of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. Consistent with this observation, the prolactin-induced increase in catecholamine synthesis was abolished by inhibitors of protein kinase A and protein kinase C (PKC). Prolactin incubation also resulted in a PKC-dependent activation of the MAPK pathway, although this was not required for the stimulation of catecholamine synthesis. In addition to increasing TH phosphorylation and catecholamine synthesis, prolactin also increased TH mRNA expression. In contrast to catecholamine synthesis, this latter response was not suppressed by inhibition of protein kinase A or PKC. These results indicate that although prolactin controls catecholamine synthesis in NEDA neurons by regulating both TH activity and TH mRNA expression, it employs distinct, nonoverlapping, signaling pathways to achieve these ends.

Dual-phase CT angiography of the normal canine portal and hepatic vasculature.

A dual-phase computed tomography (CT) angiographic technique was developed to image the hepatic and portal vascular systems using a nonselective peripheral injection of contrast medium. The arterial phase of the dual-phase scan imaged the hepatic arteries and veins, and the portal phase imaged the portal vein as well as its tributaries and branches. There were three steps involved in acquiring the dual-phase scan: a survey helical scan for orientation, a dynamic scan for timing, and finally the dual-phase helical scan. Five normal dogs were imaged using a helical scan technique. The timing of the arterial and portal phases of the scan was calculated using time vs. attenuation graphs generated from a dynamic scan. The median time of appearance of contrast medium in the cranial abdominal aorta was 8.6 s and the median time of appearance of contrast medium in the hepatic artery occurred 0.4 s later. The median time of peak enhancement in the cranial abdominal aorta was 12.0 s. The median time of appearance of contrast medium in the portal vein was 14.6 s and median time of peak enhancement was 33.0 s. The dual-phase scans provided excellent vascular opacification. The hepatic arteries, hepatic veins, cranial and caudal mesenteric veins, splenic vein, gastroduodenal vein, and portal vein branches were all consistently well defined. Dual-phase CT angiography is a minimally invasive technique which provides an excellent three-dimensional representation of portal and hepatic vascular anatomy.

Activation of erbB-1 Signaling in Tanycytes of the Median Eminence Stimulates Transforming Growth Factor β1Release via Prostaglandin E2Production and Induces Cell Plasticity

The activation of transforming growth factor alpha (TGFalpha)-erbB-1 and neuregulin-erbB-4 signaling pathways in hypothalamic astrocytes has been shown to play a key role in the process by which the neuroendocrine brain controls luteinizing hormone-releasing hormone (LHRH) secretion. Earlier studies suggested that tanycytes, an ependymoglial cell type of the median eminence, regulate LHRH release during the estrous cycle by undergoing plastic changes that alternatively allow or prevent direct access of the LHRH nerve terminals to the portal vasculature. Neither the molecules responsible for these plastic changes nor the underlying controlling mechanisms have been identified. Here we show that cultured tanycytes express erbB-1 and erbB-2, two of the four members of the erbB receptor family, and respond to TGFalpha with receptor phosphorylation, release of prostaglandin E2 (PGE2), and a PGE2-dependent increase in the release of TGFbeta1, a growth factor previously implicated in the glial control of LHRH secretion. Blockade of either erbB-1 receptor signal transduction or prostaglandin synthesis prevented the stimulatory effect of TGFalpha on both PGE2 and TGFbeta1 release. Time-lapse studies revealed that TGFalpha and TGFbeta1 have dramatically opposite effects on tanycyte plasticity. Whereas TGFalpha promotes tanycytic outgrowth, TGFbeta1 elicits retraction of tanycytic processes. Blockade of metalloproteinase activity abolished the effect of TGFbeta1, suggesting that TGFbeta1 induces tanycytic retraction by facilitating dissolution of the extracellular matrix. Prolonged (>12 hr) exposure of tanycytes to TGFalpha resulted in focal tanycytic retraction, an effect that was abolished by immunoneutralization of TGFbeta1 action, indicating that the retraction was attributable to TGFalpha-induced TGFbeta1 formation. These in vitro results identify tanycytes as targets of TGFalpha action and demonstrate that activation of erbB-1-mediated signaling in these cells results in plastic changes that, involving PGE2 and TGFbeta1 as downstream effectors, mimic the morphological plasticity displayed by tanycytes during the hours encompassing the preovulatory surge of LHRH.

Use of intraoperative mesenteric portovenography in congenital portosystemic shunt surgery.

A retrospective study of the use of intraoperative mesenteric portovenography (IOMP) in the surgical management of congenital portosystemic shunts in 100 dogs and cats was performed. Each portovenogram was scored using a subjective visual analogue scale (VAS) and was assessed for the presence of portal atresia or hypoplasia. VAS scores and portal hypoplasia assessments were obtained for portovenogram images obtained for each animal both before shunt manipulation (preligation) and following the temporary, complete ligation of the vessel (postligation). In each patient, surgical records were reviewed to ascertain the degree of shunt attenuation that was achieved at surgery. Hepatic portal vasculature was significantly different on postligation compared with preligation IOMP. Sixty-two percent of animals had apparent portal hypoplasia or atresia on their preligation IOMP. The majority of these (81%) had an improvement in portal vasculature on postligation IOMP. It was concluded that both preligation and postligation IOMP provided valuable information regarding the morphology of congenital portosystemic shunts. An accurate assessment of an animal's portal vasculature could only be made following the interpretation of a postligation portovenogram, and these findings significantly influenced the surgical management of the patient. Although individuals with high postligation VAS scores were more likely to achieve full shunt attenuation at surgery, there was no quantifiable relationship between IOMP findings and the degree of shunt attenuation achieved.

Neurophysiology of puberty

Puberty is the stage of development during which an individual first becomes capable of reproducing sexually and is characterized by maturation of the genital organs, the development of secondary sexual characteristics, and changes in mood and behavior. Although puberty is a phase of development, an introduction to the neurophysiology of the process is facilitated by a review of the essential features of the central neural control of the ovary and testis in the adult. In sexually mature individuals, the processes of ovulation, spermatogenesis, and sex steroid production are regulated by the pituitary gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). The synthesis and secretion of the pituitary gonadotropins, in turn, are governed by the brain peptide gonadotropin-releasing hormone (GnRH), which is secreted by nerve terminals in the base of the forebrain into a specialized portal circulation subserving the pituitary gland. GnRH is not secreted continuously into the portal vasculature but instead is released as intermittent discharges with a frequency of approximately one pulse every 1 to 3 h. This pulsatile mode of GnRH release by the brain is absolutely essential for sustained gonadotropin secretion, and when GnRH stimulation of the pituitary is continuous, LH and FSH release is greatly reduced. As may be predicted from the foregoing considerations, if pulsatile secretion of GnRH by the brain of men and women is interrupted, as may be the case in highly trained ballerinas and female athletes or severely undernourished individuals, pituitary gonadotropin secretion is impaired and gonadal function arrested. Thus, the GnRH pulse-generating mechanism in the brain occupies a position of primacy in the control of reproduction in the adult. Moreover, the proximal trigger activating the pituitary gonadal axis at puberty is an increase in pulsatile GnRH release in association with a modest increase in the drive to express the gene encoding this neuropeptide. For the foregoing reasons, a consideration of the mechanisms underlying the pulsatile secretion of this brain hormone in the adult provides a point of departure for a discussion of the neurophysiology of puberty.

A liver perfusion model for studies of selective adherence and transient halting of portal blood leukocytes in sinusoids

Portal blood leukocytes play an important, but still poorly defined, role in the immune processes of the liver. In our previous studies, we showed that certain leukocyte subsets are selectively halted in the liver. These cells marginate in sinusoids and, together with resident Kupffer and endothelial sinusoidal cells, participate in antiviral and antitumor processes. The molecular mechanisms of margination and cooperation with resident sinusoidal cells require clarification. However, in vivo harvesting of portal blood leukocytes is associated with cumbersome cannulation of portal and hepatic veins and manipulation of the liver, causing major disturbances in splanchnic blood flow and liver blood supply, totally distorting sinusoidal blood perfusion and leukocyte margination. To overcome these difficulties, we have developed an in situ normothermic rat liver perfusion model permitting quantitative observations of blood leukocyte extraction in sinusoids. First, liver was flushed through the portal vein and the effluent leukocytes, named liver-associated leukocytes (LAL1), were collected from hepatic veins. Then, the liver was perfused for 60 min with 50 ml of blood using a semiclosed perfusion system. Upon completion of perfusion, the liver portal vasculature was flushed again to retrieve the leukocytes extracted from the perfusing blood (LAL2). These cells were characterized with respect to their phenotype and cytotoxicity. The mean leukocyte count of the washout before perfusion was 1.04±0.2×10 6/g of liver tissue and 0.9±0.1×10 6/g after 60 min of perfusion, indicating retention by the perfused liver, the live leukocyte extracting capacity. To further evaluate the efficiency of perfusion, FITC-labelled leukocytes were added to the perfusing leukocyte-free blood. Around 95% of the postperfusion washout LALs were FITC +. Heat-killed leukocytes did not marginate in sinusoids. Preincubation of leukocytes with substances able to lower adhesion capacity, such as lidocaine, trypsin and AAGM1, significantly decreased the postperfusion LAL2 washout population. The numbers of extracted postperfusion LAL2 CD5 +, CD4 +, CD8 +, CD56 + and class II + subsets did not differ statistically from those of preperfusion LAL1. Moreover, the cytotoxicity of LAL2 and LAL1 against CC531 and K562 remained at a similar level. Thus, perfused liver also retained its selective leukocyte extraction capacity. This model shows that the process of selective margination of portal blood cell subsets in the liver can be studied in an artificially perfused liver subject to physiological blood flow parameters, temperature, oxygenation and minimal ischemic time before connection to the perfusion device. Furthermore, it is suitable for studies of the selective recruitment of blood cells in sinusoids in a wide large of situations including liver tumors, infections, rejection after transplantation, graft vs. host disease, as well as in the investigation of the effect of drugs on these processes.

Regulation of cyclooxygenase and nitric oxide synthase after discontinue of chronic inhibition of nitric oxide synthase in portal hypertensive vasculature

Regulation of cyclooxygenase and nitric oxide synthase after discontinue of chronic inhibition of nitric oxide synthase in portal hypertensive vasculature

Hepatic arterial perfusion decreases intrahepatic shunting and maintains glucose uptake in the rat liver.

Intrahepatic shunts have an important function in the regulation of portal venous pressure in the normal rat liver. The present study determined their location, the region of confluence between the hepatic arterial and portal venous vasculatures, regions within the liver that are bypassed and the effects of hepatic arterial perfusion upon the intrahepatic redistribution of portal venous flow. Livers of male Sprague-Dawley rats were excised and perfused in vitro. Hepatic bromosulphthalein (BSP) and glucose uptake were measured in hepatic venous samples. Diversion of the hepatic arterial supply into the portal venous vasculature opened the portal venous intrahepatic shunts and resulted in a 50% reduction in portal venous glucose uptake from 29.6+/-1.6% to 14.9+/-0.9% ( P<0.0001 Student's paired t-test). Portal venous injection of 15-microm-diameter microspheres also opened the intrahepatic shunts and reduced portal venous glucose uptake to 10% from 29.0+/-1.6% to 7.8+/-0.9% ( P<0.0001 Student's paired t-test). No significant reductions in portal venous BSP uptake (43.0+/-6.9 to 48.0+/-4.8%) or hepatic arterial glucose uptake, from an average value of 94.0%, occurred. Therefore, cessation of hepatic arterial perfusion or portal venous injection of microspheres reduced portal venous glucose uptake without affecting BSP uptake. It is concluded that intrahepatic shunts divert perfusate away from the perivenous, sinusoidal (zone III) regions and into the hepatic venous vasculature, distal to zone III. The microsphere data indicate that confluence between the hepatic arterial and portal venous vasculatures occurs mainly in sinusoidal zone II.

Glial-neuronal-endothelial interactions are involved in the control of GnRH secretion.

In recent years compelling evidence has been provided that cell-cell interactions involving non-neuronal cells, such as glial and endothelial cells, are important in regulating the secretion of GnRH, the neuropeptide that controls both sexual development and adult reproductive function. Modification of the anatomical relationship that exist between GnRH nerve endings and glial cell processes in the external zone of the median eminence modulates the access of GnRH nerve terminals to the portal vasculature during the oestrous cycle. The establishment of direct neuro-haemal junctions between GnRH neuroendocrine terminals and the portal vasculature on the day of pro-oestrus may be critical for the transfer of GnRH upon its release into the fenestrated capillaries of the median eminence. Notwithstanding the importance of these plastic rearrangements, glial and endothelial cells also regulate GnRH neuronal function via specific cell-cell signalling molecules. While endothelial cells of the median eminence use nitric oxide to effect this regulatory control, astrocytes employ several growth factors, and in particular those of the EGF family and their erbB receptors to facilitate GnRH release during sexual development. Loss of function of each of these erbB receptors involved in the astroglial control of GnRH secretion leads to delayed sexual development. It is clear that regulation of GnRH secretion by cell-cell communication mechanisms other than transsynaptic inputs is an important component of the central neuroendocrine process controlling mammalian reproduction.

Gonadotropin-releasing hormone (GnRH) neurons: gene expression and neuroanatomical studies

Publisher Summary Gonadotropin-releasing hormone (GnRH) neurons are the key cells regulating reproductive function in all vertebrate organisms. In mammals, birds, reptiles, and amphibians, the GnRH-1 decapeptide is released in a pulsatile manner from neuroterminals in the median eminence into the portal capillary vasculature, where it binds to receptors located on pituitary gonadotropes to regulate the synthesis and secretion of the gonadotropins. The chapter discusses the regulation of GnRH gene expression. The regulation of GnRH-1 neurons involves alterations in gene expression and neuroanatomical inputs. GnRH gene expression changes in response to stimuli, such as steroid hormone feedback, varies across the estrous cycle, and changes across the reproductive life cycle, particularly during pubertal maturation and reproductive aging. The most dramatic alterations in GnRH mRNA levels are seen during reproductive development in association with the pubertal process. The studies on the mechanisms for the regulation of GnRH mRNA levels suggest that a post-transcriptional process, involving an alteration in GnRH mRNA stability, possibly mediated by the GnRH poly (A) tail length, may be the primary one responsible for the control of GnRH mRNA levels.

Anatomy of the patent ductus venosus in the cat

The biplanar mesenteric vein portovenograms of 10 cats with left divisional intrahepatic portosystemic shunts consistent with a patent ductus venosus (PDV) were reviewed. A corrosion cast of the hepatic portal vasculature was made post mortem from one individual that died post operatively following surgical attenuation of the shunting vessel. On the basis of the combined surgical, post mortem and imaging data, these left divisional shunts were found to have consistent anatomy, each having a straight vessel which drained into a venous ampulla before draining into the caudal vena cava at the level of the diaphragm. The left phrenic vein and left hepatic vein both entered the ampulla independently of the shunting vessel. The anatomical similarity between these findings in the cat and the PDV in the dog suggest that it is appropriate to describe this particular portosystemic shunt as a PDV.

Hepatic arterial perfusion regulates portal venous flow between hepatic sinusoids and intrahepatic shunts in the normal rat liver in vitro.

Intrahepatic shunts regulate portal venous pressure during periods of acute portal hypertension when the transhepatic portal resistance is momentarily increased in the normal rat liver in vivo. Hepatic arterial inflow may also increase the transhepatic portal resistance and activate intrahepatic shunts. In the present study, the transhepatic portal resistance and the activity of intra-hepatic shunts were measured in vitro and the point of confluence between the hepatic artery and portal vein in the rat determined. Livers of male Sprague-Dawley rats were single-pass, dual-perfused in vitro. Total cessation or diversion of the hepatic arterial inflow to the portal venous vasculature, whilst maintaining total hepatic perfusate flow, decreased intrasinusoidal pressure, increased transhepatic portal venous resistance and opened the portal venous intrahepatic shunts in a manner similar to intraportal injection of 15-microm diameter microspheres. Injections of the microspheres into the hepatic arterial circulation increased hepatic arterial pressure dramatically, consistent with complete occlusion of the arterial vasculature. The intrahepatic shunts are located at a pre-sinusoidal level because no increases were detected in hepatic arterial pressure following intraportal injection of microspheres. The hepatic arterial vasculature, unlike the portal supply, does not possess a collateral shunt circulation and coalesces with the portal vein at an intrasinusoidal location

Dopamine transporters participate in the physiological regulation of prolactin.

Three populations of hypothalamic neuroendocrine dopaminergic (NEDA) neurons, arising from the arcuate and periventricular nuclei of the hypothalamus release dopamine (DA) that acts at the pituitary gland to regulate the secretion of PRL. It is generally accepted that NEDA neurons lack functional DA transporters (DATs), which are responsible for uptake of DA from the synaptic cleft into the presynaptic axon terminal. This study localized DATs to the hypothalamo-pituitary axis and evaluated the effect of DAT blockade on the hypothalamo-pituitary regulation of PRL. After 7 days of treatment with cocaine (a nonspecific amine transporter blocker) or mazindol (a specific DAT blocker), the relative abundance of PRL messenger RNA (mRNA) in the anterior lobe (AL) of OVX rats was significantly decreased, whereas the relative abundance of tyrosine hydroxylase mRNA in the hypothalamus was significantly increased. The effect of cocaine or mazindol administration on DA turnover and serum PRL concentration was examined in estradiol (E2)-treated OVX rats. E2 administration (i.v.) resulted in a significant increase in serum PRL within 4 h; however, cocaine or mazindol administration abolished the E2-induced increase of PRL. Cocaine or mazindol significantly increased the concentration of DA at the site of the axon terminals within the median eminence (ME), intermediate lobe (IL) and neural lobe (NL), indicating blockade of uptake. Because formation of DOPAC requires uptake of DA, concentrations of DOPAC in the ME, IL and NL decreased following treatment with either cocaine or mazindol. These data, together with the presence of immunopositive DAT in the ME, pituitary stalk, IL, and NL, suggest that a functional DAT system is present within all three populations of NEDA neurons. Moreover, similarity between the effects of cocaine and mazindol treatment indicate that blockade of the DAT, but not other amine transporters, is responsible for suppression of PRL gene expression and secretion. Blockade of DATs prevent uptake of DA into NEDA neurons and consequently increases the amount of DA that diffuses into the portal vasculature and reaches the AL. These data provide evidence that DATs play a physiological role in the regulation of DA release from and TH expression in NEDA neurons and consequently PRL secretion and PRL gene expression and further support our previous observation that the regulation of PRL secretion involves all three populations of NEDA neurons.

Nitric oxide inhibits norepinephrine-induced hepatic vascular responses but potentiates hepatic glucose output

We previously reported that sympathetic nerve-induced vasoconstriction in the intestine resulted in shear stress induced release of nitric oxide (NO) that led to presynaptic inhibition of transmitter release. In contrast, studies in the liver suggested a postsynaptic inhibition of vascular responses, thus leading to the hypothesis tested here that maintained catecholamine release in the liver would result in maintained metabolic catecholamine action in the face of inhibition of vascular responses. In rats, norepinephrine (NE) induced elevations in arterial glucose content were inhibited by NO synthase antagonism (Nω-nitro-L-arginine methyl ester (L-NAME), 10 mg/kg, intraportal) but potentiated by NO donor administration (3-morpholinosydnonimine (SIN-1), 0.2 mg/kg, intraportal). The potentiated effect of SIN-1 was abolished by indomethacin (7.5 mg/kg, intraportal). To confirm the hepatic site of metabolic effect, cats were used so that blood flow and hepatic glucose balance could be determined. SIN-1 potentiated NE-induced glucose output from the liver from 5.0 ± 0.4 to 7.2 ± 0.6 mg·min-1·kg-1. The potentiation was blocked by methylene blue, a guanylate cyclase inhibitor. Contrary to the glucose response, L-NAME potentiated but SIN-1 attenuated NE-induced portal vasoconstriction. Thus NO is shown to produce differential modulation of vascular and metabolic effects of NE. Vasoconstriction of the hepatic vasculature is inhibited by NO, whereas the glycogenolytic response to NE is potentiated, responses that are probably mediated by prostaglandin.Key words: prostaglandin, glucose, portal vasculature, Nω-nitro-L-arginine methyl ester, 3-morpholinosydnonimine.

Hemodynamics of the ductus venosus

Although the ductus venosus has a similar function in human as in animal pregnancies (to regulate the shunting of oxygenated blood from the umbilical vein towards the left atrium), the amount of blood shunted in the human fetus seems to be less (25–40%) than in the animal (50%). The degree of shunting depends both on the resistance of the portal vasculature in the liver as well as the resistance of the ductus venosus itself. Neural and endocrine regulation plays a role in this distribution, as do fluid mechanical forces; blood viscosity and umbilical venous pressure are powerful determinants. There is a high degree of shunting at reduced umbilical venous pressure, and by increasing hematocrit, and viscosity, the distribution shifts from the liver to the ductus venosus. Additionally, the ductus venosus acts as transmission line in the opposite direction for the atrial pressure waves. Shape, viscosity, compliance, and particularly the diameter of the inlet are suggested to influence the pulsatility of the blood velocity at the ductus venosus inlet – and determine the degree of wave transmission into the umbilical vein. Occurrence of umbilical venous pulsation, an important diagnostic sign, is also dependent upon the size and compliance of the umbilical vein.

Can GHRH or GH secretagogues re-initiate pituitary GH pulsatility?

Can GHRH or GH secretagogues re-initiate pituitary GH pulsatility?