Modulation of sympathoadrenergic contractions by perivascular adipose tissue in mesenteric arteries of rats with different level of body adiposity.

Obesity is associated with increased sympathetic nervous system activation, possibly contributing to higher cardiovascular risk. The aim of this study was to assess the relationship between body adiposity and sympathoadrenergic contractions in rat isolated mesenteric arteries, and the modulatory effect of mesenteric perivascular adipose tissue (PVAT). Experiments were performed on male 38-week-old Wistar, Zucker lean (ZL) and Zucker diabetic fatty (ZDF) rats. Paired rings of isolated rat superior mesenteric arteries with or without PVAT were prepared and connected to a force-displacement transducer for the recording of isometric tension. Contractile responses were elicited by increasing doses of exogenous noradrenaline and by endogenous noradrenaline released during electrical stimulation of perivascular adrenergic nerves. In ZDF rats, mesenteric PVAT had marked anticontractile effect leading to significant reduction in adrenergic contractions of their superior mesenteric arteries; however, in arterial preparations without PVAT, obese rats showed significantly increased sensitivity in their contractile responses to adrenergic stimulation when compared to other rat groups. In Wistar rats, ranging in the level of body adiposity between ZL and ZDF rats, neurogenic contractions in arterial preparations with preserved PVAT were higher compared to those without PVAT. No vasomodulatory effect of PVAT was detected in mesenteric arteries from ZL rats. The results of this study indicate that the modulatory effect of mesenteric PVAT on arterial adrenergic contractions did not change in proportion with increasing adiposity; however, it could be influenced by the rat strain-specific distribution of sympathetic nerves between PVAT and the proper mesenteric arterial wall. In ZDF rats, characterized by higher vascular sympathetic tone, the mesenteric arteries might be specifically regulated by the anticontractile effect of PVAT, leading to higher mesenteric blood flow. This could be associated with hyperphagia and increased nutrient-induced mesenteric vasodilatation in this rat strain.

Functional circuitry of neuro-immune communication in the mesenteric lymph node and spleen.

The peripheral nervous system is an active participant in immune responses capable of blocking aberrant activation of a variety of immune cells. As one of these neuro-immune circuits, the cholinergic anti-inflammatory pathway has been well established to reduce the severity of several immunopathologies. While the activation of this pathway by vagal nerve stimulation requires sympathetic innervation of the spleen, the neuro-immune circuitry remains highly controversial. Neuro-immune pathways in other lymphoid tissues such as mesenteric lymph nodes (MLN) that are critical to the surveillance of the small intestine and proximal colon have not been assessed. Using conditionally expressed Channelrhodopsin, selective stimulation of sympathetic post-ganglionic neurons in the superior mesenteric ganglion (SMG) prevented macrophage activation and LPS-induced TNFα production in the spleen and MLN, but not in the inguinal LN. Site selective stimulation of the SMG induced the release of norepinephrine, resulting in ß2AR dependent acetylcholine release in the MLN and spleen. VNS-evoked release of norepinephrine and acetylcholine in the MLN and spleen was significantly reduced using selective optogenetic blockade applied at the SMG. Additionally, this optogenetic blockade restored LPS-induced TNFα production, despite VNS. These studies identify the superior mesenteric ganglion as a critical node in a neuro-immune circuit that can inhibit immune function in the MLN and the spleen.

The adipokine chemerin amplifies electrical field-stimulated contraction in the isolated rat superior mesenteric artery.

The adipokine chemerin causes arterial contraction and is implicated in blood pressure regulation, especially in obese subjects with elevated levels of circulating chemerin. Because chemerin is expressed in the perivascular adipose tissue (PVAT) that surrounds the sympathetic innervation of the blood vessel, we tested the hypothesis that chemerin (endogenous and exogenous) amplifies the sympathetic nervous system in mediating electrical field-stimulated (EFS) contraction. The superior mesenteric artery, with or without PVAT and with endothelium and sympathetic nerve intact, was mounted into isolated tissue baths and used for isometric contraction and stimulation. Immunohistochemistry validated a robust expression of chemerin in the PVAT surrounding the superior mesenteric artery. EFS (0.3-20 Hz) caused a frequency-dependent contraction in isolated arteries that was reduced by the chemerin receptor ChemR23 antagonist CCX832 alone (100 nM; with, but not without, PVAT), but not by the inactive congener CCX826 (100 nM). Exogenous chemerin-9 (1 µM)-amplified EFS-induced contraction in arteries (with and without PVAT) was blocked by CCX832 and the α-adrenergic receptor antagonist prazosin. CCX832 did not directly inhibit, nor did chemerin directly amplify, norepinephrine-induced contraction. Whole mount immunohistochemical experiments support colocalization of ChemR23 with the sympathetic nerve marker tyrosine hydroxylase in superior mesenteric PVAT and, to a lesser extent, in arteries and veins. These studies support the idea that exogenous chemerin modifies sympathetic nerve-mediated contraction through ChemR23 and that ChemR23 may be endogenously activated. This is significant because of the well-appreciated role of the sympathetic nervous system in blood pressure control.

[Perivascular innervation of the superior mesenteric artery: pathophysiological implications]. / Inervación perivascular de la arteria mesentérica superior: implicaciones fisiopatológicas.

INTRODUCTION: The mesenteric artery is part of the splanchnic circulation system and, due to the large amount of blood that flows through it, it is involved in the regulation of arterial pressure; to perform this function it is essential to control vascular tone. This tone is regulated by several local, metabolic, endocrine and nervous factors, the most notable of these latter being the mesenteric perivascular innervation. DEVELOPMENT: The most significant features of mesenteric perivascular innervation are described, with special attention to the sympathetic, nitrergic and sensory innervations. The article also analyses the involvement of this innervation in the pathophysiology of ageing, diabetes, arterial hypertension and splanchnic vasodilatation secondary to cirrhosis/portal hypertension. CONCLUSIONS: Mesenteric perivascular innervation plays an important role in the regulation of blood flow and arterial pressure. Alterations in this innervation are involved in the genesis and continuation of vascular disorders associated with diabetes, splanchnic vasodilatation secondary to cirrhosis/portal hypertension and also in the ageing process, by modifying the balance between vasodilator and vasoconstrictor agents. Greater knowledge of these anomalies can be used to gain a better understanding of the mechanisms involved in these disorders and to help in the design of new forms of treatment.

Otolithic activation on visceral circulation in humans: effect of aging.

Engagement of the otolith organs elicits differential activation of sympathetic nerve activity and vascular responses to muscle and skin in humans. Additionally, aging attenuates the otolith organ-mediated increases in muscle sympathetic nerve activity in older adults. In this study, we hypothesized that 1) the vestibulosympathetic reflex (VSR) would elicit visceral vascular vasoconstriction and 2) visceral vascular response to the VSR would be attenuated in older subjects compared with young. To test these hypotheses, heart rate, mean arterial blood pressure, and renal, celiac trunk, and superior mesenteric arterial blood velocity (Doppler ultrasound) were measured in 22 young (25+/-1 yr) and 18 older (65+/-2 yr) healthy subjects during head-down rotation (HDR), which selectively activates the otolith organs. Mean arterial pressure and heart rate did not change from baseline during HDR in young or older subjects. Renal blood velocity (Delta -2+/-1 cm/s) and vascular conductance (Delta -0.03+/-0.01 cm.s(-1).mmHg(-1)) significantly decreased from baseline during HDR (P<0.05) in young subjects. In contrast, renal blood velocity and conductance did not change in older subjects (Delta -0.2+/-1 cm/s and Delta0.02+/-0.08 mmHg.cm(-1).s(-1), respectively) during HDR. Superior mesenteric and celiac blood velocity and vascular conductance did not change in response to HDR in either the young or older subjects. These data suggest that renal vasoconstriction occurs during otolith organ activation in young but not older humans. Together with our previous studies, we conclude that the VSR elicits a diverse patterning of sympathetic outflow that results in heterogeneous vascular responses in humans and that these responses are significantly attenuated in older humans.

Angiotensin II type 2 receptors facilitate reinnervation of phenol-lesioned vascular calcitonin gene-related peptide-containing nerves in rat mesenteric arteries.

The present study was designed to investigate involvement of angiotensin II (Ang II) type 2 receptors (AT2 receptors) in restoration of perivascular nerve innervation injured by topical phenol treatment. Male Wistar rats underwent in vivo topical application of 10% phenol around the superior mesenteric artery. After phenol treatment, animals were subjected to immunohistochemistry of the third branch of small arteries, Western blot analysis of AT2 receptor protein expression in dorsal root ganglia (DRG) and studies of mesenteric neurogenic vasoresponsiveness. Ang II (750 ng/kg/day), nerve growth factor (NGF; 20 microg/kg/day) and PD123,319 (AT2 receptor antagonist; 10 mg/kg/day) were intraperitoneally administered for 7 days using osmotic mini-pumps immediately after topical phenol treatment. Losartan (AT1 receptor antagonist) was administered in drinking water (0.025%). Phenol treatment markedly reduced densities of both calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) and neuropeptide Y (NPY)-LI-containing fibers. NGF restored densities of both nerve fibers to the sham control level. Coadministration of Ang II and losartan significantly increased the density of CGRP-LI-fibers but not NPY-LI-fibers compared with saline control. The increase of the density of CGRP-LI-fibers by coadministration of Ang II and losartan was suppressed by adding PD123,319. Coadministration of Ang II and losartan ameliorated reduction of CGRP nerve-mediated vasodilation of perfused mesenteric arteries caused by phenol treatment. The AT2 receptor protein expression detected in DRG was markedly increased by NGF. These results suggest that selective stimulation of AT2 receptors by Ang II facilitates reinnervation of mesenteric perivascular CGRP-containing nerves injured by topical phenol application in the rat.

[Theories and techniques for resection of the extrapancreatic nerve plexus in the head of the pancreas during a Whipple procedure for carcinoma of the pancreas--suggestions from the perspective of surgical anatomy and pathology].

Although various therapeutic modalities for carcinoma of the pancreas are available, "curative (R0) resection" is the most important. Thus, the aim of surgery for carcinoma of the pancreas is local complete resection of the carcinoma. We offer two suggestions for complete resection of carcinoma of the pancreas, which shows a strong invasive tendency around nerve fibers, during a Whipple procedure. 1. En bloc resection of the right side of nerve plexus of the superior mesenteric artery and the first and second nerve plexus of the pancreatic head should be performed. It is easy to perform this procedure when the superior mesenteric artery should be moved to the right side of the superior mesenteric vein through under this vein. 2. The entire cut end of the nerve plexus should be investigated during the operation using frozen specimens and confirmed to be negative for cancer. If the cut end is positive for cancer, additional resection of the nerve plexus should be performed to achieve curative resection. The reason is that it is impossible to completely investigate positive or negative carcinoma in the cut end of the nerve plexus after surgery, since the cut end is long and some specimens are deformed by formalin fixation.

Structural and neurochemical features of postganglionic sympathetic neurons in the superior mesenteric ganglion of spontaneously hypertensive rats.

Postganglionic sympathetic neurons, which are exquisitely sensitive to small changes in levels of target-derived nerve growth factor (NGF), express two transmembrane receptors: 1) the trkA receptor mediates neuron survival and neurite outgrowth; and 2) the p75 neurotrophin receptor (p75NTR) enhances neuronal responsiveness of trkA to NGF. Elevating levels of NGF induces several morphological and neurochemical alterations in sympathetic neurons, including axonal sprouting, increased levels of p75NTR mRNA relative to trkA mRNA, and increased accumulations of NGF in hypertrophied somata. Spontaneously hypertensive rats (SHR) display both elevated NGF levels and increased sympathetic axonal innervation of the mesenteric vasculature. In this investigation we assessed whether sympathetic neurons innervating the mesenteric vasculature of SHR display other features indicative of increased levels of target-derived NGF. In 5-week-old SHR, levels of both p75NTR and trkA mRNA in mesenteric sympathetic neurons were significantly elevated compared to levels in age-matched control rats. By 15 and 30 weeks of age, levels of p75NTR mRNA expression in mesenteric sympathetic neurons were similar between SHR and control rats. Accumulations of NGF were depleted in the sympathetic somata of 15- and 30-week-old SHR compared to age-matched control rats. Moreover, sympathetic neurons in SHR were not hypertrophied, as the sizes of somata were comparable between SHR and control rats. Our data illustrate that despite having augmented levels of NGF in the mesenteric vasculature, SHR do not display many of the morphological and neurochemical features that are associated with an enhanced responsiveness by sympathetic neurons to elevated levels of target-derived NGF.

Role of female sex hormones in neuronal nitric oxide release and metabolism in rat mesenteric arteries.

This study examines the effects of female sex hormones on the vasoconstrictor response to electrical field stimulation (EFS), as well as the modulation of this response by neuronal NO. For this purpose, segments of denuded superior mesenteric artery from ovariectomized (OvX) female Sprague-Dawley rats and from control rats (in oestrus phase) were used. EFS induced frequency-dependent contractions, which were greater in segments from OvX rats than in those from control rats. The NO synthase inhibitor N(G)-nitro-l-arginine methyl ester strengthened EFS-elicited contractions to a greater extent in arteries from OvX rats than in those from control rats. Similar results were observed with the preferential neuronal NO synthase inhibitor 7-nitroindazole. The sensorial neurotoxin capsaicin did not modify EFS-induced contractions in segments from either group. In noradrenaline-precontracted segments, sodium nitroprusside (SNP) induced concentration-dependent relaxation, which was greater in segments from control rats than in those from OvX rats. 8-Bromo-cGMP induced similar concentration-dependent relaxation in noradrenaline-precontracted segments from both OvX and control rats. Diethyldithiocarbamate, a superoxide dismutase (SOD) inhibitor, reduced the relaxation induced by SNP in segments from both groups of rats. SOD, a superoxide anion scavenger, enhanced the relaxation induced by SNP in segments from OvX rats, but did not modify it in segments from control rats. EFS induced NO(-)(2) formation, which was greater in segments from OvX than in those from control rats, and pretreatment with tetrodotoxin, a blocker of nerve impulse propagation, abolished release in both cases. These results suggest that EFS induces greater neuronal NO release in mesenteric segments from OvX rats than in those from control rats and, although NO metabolism is also higher, the contribution of net neuronal NO in the vasomotor response to EFS is greater in segments from OvX rats than in those from control rats.

Identification of intestinofugal neurons projecting to the coeliac and superior mesenteric ganglia in the rat.

Intestinofugal neurons are parts of the afferent limbs of inhibitory intestino-intestinal reflexes. These neurons have been mapped in guinea-pigs, where they have a gradient of increasing frequency of occurrence from oral to anal, but not in other species. In the present work in the rat, a species that is more amenable to physiological study than the guinea-pig, we have used retrograde tracing to map the distribution of the cell bodies of intestinofugal neurons projecting to the coeliac-superior mesenteric ganglion complex. Labelled nerve cells were found in the myenteric, but not the submucosal plexus. They were mono-axonal neurons, most with Dogiel type I morphology, and were immunoreactive for choline acetyltransferase, implying that they are cholinergic, which is consistent with functional studies. The cells increased in number per unit area from the stomach, through the small intestine, to the caecum. The results are consistent with physiological studies that reveal distal to proximal inhibitory reflexes that are more potent from distal compared to proximal sites.

Cutaneous vascular bed is not involved in arterial pressure changes elicited by increasing or decreasing the activity of inhibitory vasomotor neurons in caudal ventrolateral medulla in rabbits.

We determined whether caudal ventrolateral medulla (CVLM) vasodepressor neurons tonically inhibit vasomotor tone in the ear in anesthetized rabbits. Injection of L-glutamate (10 nmol in 100 nl) into the CVLM decreased arterial pressure and increased superior mesenteric conductance. Ear conductance decreased (0.43+/-0.06 to 0. 33+/-0.05 cm s(-1) per mmHg, n=15 injections, 12 rabbits, P<0.01). Conversely, bilateral injection of gamma-aminobutyric acid (100 nmol in 100 nl) increased arterial pressure and decreased superior mesenteric conductance. At the same time ear conductance increased (0.39+/-09 to 0.48+/-0.27 cm s(-1) per mmHg, n=8 injections, eight rabbits, P<0.05). Results suggest that ear vessels are not tonically inhibited by the CVLM vasodepressor neurons. Presympathetic motoneurons regulating cutaneous flow may be excited, rather than inhibited, by the CVLM neurons.

Significant role of neuronal non-N-type calcium channels in the sympathetic neurogenic contraction of rat mesenteric artery.

1. The possible involvement of pre-junctional non-N-type Ca2+ channels in noradrenaline (NA)-mediated neurogenic contraction by electrical field stimulation (EFS) was examined pharmacomechanically in the isolated rat mesenteric artery. 2. EFS-generated contraction of endothelium-denuded mesenteric artery was frequency-dependent (2 - 32 Hz) and was abolished by tetrodotoxin (TTX, 1 microM), guanethidine (5 microM) or prazosin (100 nM), indicating that NA released from sympathetic nerve endings mediates the contractile response. 3. NA-mediated neurogenic contractions to lower frequency stimulations (2 - 8 Hz) were almost abolished by an N-type Ca2+ channel blocker, omega-conotoxin-GVIA (1 microM) whereas the responses to higher frequency stimulations (12 - 32 Hz) were less sensitive to omega-conotoxin-GVIA. The omega-conotoxin-GVIA-resistant component of the contractile response to 32 Hz stimulation was inhibited partly (10 - 20%) by omega-agatoxin-IVA (10 - 100 nM; concentrations which are relatively selective for P-type channels) and to a greater extent by omega-agatoxin-IVA (1 microM) and omega-conotoxin-MVIIC (3 microM), both of which block Q-type channels at the concentrations used. 4. omega-Agatoxin-IVA (10 - 100 nM) alone inhibited 32 Hz EFS-induced contraction by 10 approximately 20% whereas omega-conotoxin-MVIIC (3 microM) alone inhibited the response by approximately 60%. 5. These omega-toxin treatments did not affect the contractions evoked by exogenously applied NA. 6. These findings show that P- and Q-type as well as N-type Ca2+ channels are involved in the sympathetic neurogenic vascular contraction, and suggest the significant role of non-N-type Ca2+ channels in NA release from adrenergic nerve endings when higher frequency stimulations are applied to the nerve.

Kynurenic acid inhibits circulatory responses to intracisternally injected L-proline in conscious rats.

To investigate the modes of action of potential neurotransmitters for cardiovascular control, amino acids and an antagonist were injected intracisternally into conscious rats. Blood pressure and superior mesenteric flow were measured with cannulae and electromagnetic flow probes that had been implanted in a previous operation under pentobarbitone anaesthesia. L-Proline, L-glutamate and L-arginine (10, 2 and 10 micromol, respectively) caused similar increases in blood pressure and mesenteric vascular resistance. Prior injection of kynurenic acid (0.1 micromol), a broad spectrum antagonist of ionotropic excitatory amino acid receptors, completely blocked the circulatory effects of L-proline, significantly reduced those of L-glutamate but had little effect on responses to L-arginine. These results suggest that the central pressor pathways activated by L-proline, a potential endogenous neurotransmitter, are mediated by ionotropic excitatory amino acid receptors.

Neurally-mediated vasodilatation in normal and portal hypertensive rats: role of nitric oxide and calcitonin gene-related peptide.

BACKGROUND/AIMS: Portal hypertension is associated with systemic vasodilatation and vascular hyporeactivity, and is reversed by inhibiting nitric oxide biosynthesis. Nitric oxide and calcitonin gene-related peptide are neurotransmitters of non-adrenergic non-cholinergic nerves. The role of nitric oxide and calcitonin gene-related peptide in nerve-stimulated vasodilatation in portal hypertension is unknown. METHODS: We tested (i) if in vitro perfused superior mesenteric arterial vascular beds of portal hypertensive rats (induced by partial portal vein ligation) showed an increased vasodilatation to periarterial nerve stimulation compared to normal controls, and (ii) if this vasodilatation was modulated by nitric oxide and calcitonin gene-related peptide antagonism. RESULTS: Vasodilatatory responses to periarterial nerve stimulation (10 V, 1 ms) with increasing frequencies (Hertz, 2-12) in preconstricted vessels (methoxamine and guanethidine) were significantly smaller in vessel preparations of control (n=8) compared to portal hypertensive (n=7) rats, values with 8 Hertz being 32.3+/-3.6% and 44.9+/-3.6%, respectively (p<0.05). This difference was reversed by inhibiting nitric oxide and calcitonin gene-related peptide action with the nitric oxide-biosynthesis inhibitor N(omega)-Nitro-L-arginine, values for 8 Hertz being 28.7+/-4.8% (controls) and 37.8+/-3.3% (portal hypertensive, ns) or with the calcitonin gene-related peptide antagonist CGRP8-37, values being 25.2+/-2.8% (controls) and 27.8+/-4.2% (portal hypertensive, ns), respectively (n=4-6 per group). Vasodilatation to the beta-agonist isoproterenol was not significantly different between groups with and without calcitonin gene-related peptide and nitric oxide antagonism. CONCLUSION: Portal hypertensive rats display a significantly enhanced vasodilatation to periarterial nerve stimulation, which is reversed by inhibiting the non-adrenergic non-cholinergic neurotransmitters nitric oxide and especially calcitonin gene-related peptide.

[Reactivity of isolated arteries: the role of their dynamic stretching]. / Reaktivnost' izolirovannykh arterii: rol' ikh dinamicheskogo rastiazheniia.

The smooth muscle constriction elicited by the NA or EFS was smaller when static stretching was replaced with a dynamic one in rats. The latter seems to activate the NO synthesis/secretion thus inhibiting the constriction and potentiating the dilation.

Central role of heterocellular gap junctional communication in endothelium-dependent relaxations of rabbit arteries.

1. The contribution of gap junctions to endothelium-dependent relaxation was investigated in isolated rabbit conduit artery preparations pre-constricted by 10 microM phenylephrine (PhE). 2. Acetylcholine (ACh) relaxed the thoracic aorta by approximately 60 % and the superior mesenteric artery (SMA) by approximately 90 %. A peptide possessing sequence homology with extracellular loop 2 of connexin 43 (Gap 27, 300 microM) inhibited relaxation by approximately 40 % in both artery types. Gap 27 also attenuated the endothelium-dependent component of the relaxation induced by ATP in thoracic aorta but did not modify force development in response to PhE. 3. NG-nitro-L-arginine methyl ester (L-NAME, 300 microM), an inhibitor of NO synthase, attenuated ACh-induced relaxation by approximately 90 % in the aorta but only by approximately 40 % in SMA (P < 0.05). Residual L-NAME-insensitive relaxations were almost abolished by 300 microM Gap 27 in aorta and inhibited in a concentration-dependent fashion in SMA (approximately 50 % at 100 microM and approximately 80 % at 10 mM). Gap 27 similarly attenuated the endothelium-dependent component of L-NAME-insensitive relaxations to ATP in aorta. 4. Responses to cyclopiazonic acid, which stimulates endothelium-dependent relaxation through a receptor-independent mechanism, were also attenuated by Gap 27, whereas this peptide exerted no effect on the NO-mediated relaxation induced by sodium nitroprusside in preparations denuded of endothelium. 5. ACh-induced relaxation of 'sandwich' mounts of aorta or SMA were unaffected by Gap 27 but completely abolished by L-NAME. 6. We conclude that direct heterocellular communication between the endothelium and smooth muscle contributes to endothelium-dependent relaxations evoked by both receptor-dependent and -independent mechanisms. The inhibitory effects of Gap 27 peptide do not involve homocellular communication within the vessel wall or modulation of NO release or action.

Potentiality of dissection of the lymph nodes with preservation of the nerve plexus around the superior mesenteric artery.

BACKGROUND/AIMS: Periampullary cancer frequently metastasizes to the lymph nodes around the superior mesenteric artery. Simultaneous dissection of the nerve plexus around the SMA, however, often results in intractable diarrhea. This study was performed to examine the extent to which regional lymph nodes may be dissected while preserving the superior mesenteric nerve plexus during radical surgery for periampullary cancer. METHODOLOGY: The pancreas and surrounding tissue from ten adult autopsied subjects were sectioned at 5 mm intervals. The structure of the nerve plexus and the distribution of the lymph nodes were analyzed, and the anatomical relationship between the nodes and the nerve plexus was investigated. RESULTS: The average thickness of the PLsma was 4.2 +/- 1.3 mm, becoming thinner from the root to the periphery. The lymph nodes were distributed uniformly on the right and left hemicircles of the superior mesenteric artery and along its longitudinal axis. The average number of lymph nodes was 14.2 +/- 7.5 per subject, and the average maximum node diameter was 3.3 +/- 2.3 mm. The distance from the adventitia of the superior mesenteric artery to the node was 5.5 +/- 2.0 mm. Of a total of 142 lymph nodes, 134 (94.4%) were located outside of the nerve plexus. CONCLUSION: Dissection of the superior mesenteric lymph nodes while preserving the superior mesenteric nerve plexus is theoretically possible.

Impact of age on modulation of norepinephrine release from sympathetic nerves in the rat superior mesentery artery.

There is an age-related increase in stimulation-evoked fractional norepinephrine release in tail arteries of Fischer 344 rats from 6-20 months of age. Previous studies have ruled out changes in the function of uptake and subsequent metabolism mechanisms, or feedback by prejunctional alpha2-adrenoceptors. The tail artery is important in thermoregulation, and there is the possibility that the previously observed increase in sympathetic nerve activity is due to age-related changes in thermoregulation as opposed to a fundamental age-related change in the regulation of sympathetic nerves. Thus, we measured stimulation-evoked norepinephrine release in another blood vessel model, the superior mesentery artery using HPLC with electrochemical detection. In this study fractional norepinephrine release was measured under three separate conditions, drug free Krebs'; in the presence of deoxycorticosterone and cocaine; in the presence of deoxycorticosterone and cocaine and the alpha2-adrenergic receptor antagonist, idazoxan. The most significant finding was that fractional norepinephrine release in mesentery arteries from 20-month-old animals was higher as compared to 6 months regardless of treatment condition. Furthermore, the elevation in norepinephrine release cannot be accounted for by changes in norepinephrine content, uptake and subsequent metabolism mechanisms or changes in basal norepinephrine release. These data from the mesentery artery model confirm and support our previous work in the rat tail artery model. In addition, the data from this study suggest the possibility that there are common mechanisms underlying the age-related increase in peripheral sympathetic nerve activity.

Quantitative analysis of calcitonin gene-related peptide- and neuropeptide Y-immunoreactive nerve fibers in mesenteric blood vessels of rats irradiated with cobalt-60 gamma rays.

The effects of 60Co gamma rays on calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers and neuropeptide Y (NPY)-immunoreactive nerve fibers were examined in mesenteric blood vessels of rats. Using a free-floating immunostaining streptavidin-biotin peroxidase complex method combined with a nickel-enhancement technique, we found that the distribution pattern of these two peptidergic nerve fibers in superior mesenteric arteries and superior mesenteric veins did not change, while the densities of CGRP-immunoreactive nerve fibers and NPY-immunoreactive nerve fibers in superior mesenteric arteries and veins varied with the time after irradiation. The results suggested that CGRP and NPY may be important in the development and elimination of radiation-induced injury.