Potassium turnover and norepinephrine sensitivity in the thoracic aorta of the Dahl rat

This in vitro study evaluated the basal 42K turnover and response to norepinephrine (NE) in the thoracic aorta removed from Dahl salt-sensitive (S) and salt-resistant (R) rats. Five-week-old S and R rats were placed on either a high-salt (HS) or low-salt (LS) diet. After 5 weeks of the diet, systolic blood pressure, aortic weight/length ratio, and the cellular pool of K+ were elevated in the S-HS group only. In contrast, the steady state turnover of 42K, the NE ED50, and the response to a supramaximal dose of NE were the same in both groups of salt-sensitive and salt-resistant rats. These results suggest that, despite the presence of a greatly elevated systolic blood pressure and evidence of aortic hypertrophy, the intrinsic electrolyte metabolism of the vascular smooth muscle in the Dahl hypertensive rat is the same as that of the Dahl normotensive rat.     

Neural influences on sonic hedgehog and apoptosis in the rat penis

The role of sonic hedgehog (SHH) in maintaining corpora cavernosal morphology in the adult penis has been established; however, the mechanism of how SHH itself is regulated remains unclear. Since decreased SHH protein is a cause of smooth muscle apoptosis and erectile dysfunction (ED) in the penis, and SHH treatment can suppress cavernous nerve (CN) injury-induced apoptosis, the question of how SHH signaling is regulated is significant. It is likely that neural input is involved in this process since two models of neuropathy-induced ED exhibit decreased SHH protein and increased apoptosis in the penis. We propose the hypothesis that SHH abundance in the corpora cavernosa is regulated by SHH signaling in the pelvic ganglia, neural activity, or neural transport of a trophic factor from the pelvic ganglia to the corpora. We have examined each of these potential mechanisms. SHH inhibition in the penis shows a 12-fold increase in smooth muscle apoptosis. SHH inhibition in the pelvic ganglia causes significantly increased apoptosis (1.3-fold) and decreased SHH protein (1.1-fold) in the corpora cavernosa. SHH protein is not transported by the CN. Colchicine treatment of the CN resulted in significantly increased smooth muscle apoptosis (1.2-fold) and decreased SHH protein (1.3-fold) in the penis. Lidocaine treatment of the CN caused a similar increase in apoptosis (1.6-fold) and decrease in SHH protein (1.3-fold) in the penis. These results show that neural activity and a trophic factor from the pelvic ganglia/CN are necessary to regulate SHH protein and smooth muscle abundance in the penis.     

Possible interactions between neurotensin and prostaglandins in the isolated rat portal vein

Neurotensin (NT) was found to elicit a dose-dependent contractile effect in the isolated rat portal vein. This effect was not inhibited by phentolamine, atropine, methysergide, a mixture of diphenhydramine and cimetidine, or by [Leu⁸]-angiotensin II, but it was markedly reduced or abolished by various antiinflammatory drugs such as indomethacin, acetylsalicylic acid, mefenamic acid, hydrocortisone and by mepacrine, an inhibitor of phospholipase A₂. The concentrations of antiinflammatory drugs used to inhibit NT, also antagonized the venoconstrictor effects of bradykinin and angiotensin, but did not affect the responses of the vein to noradrenaline. [D-Trp¹¹]-NT, a previously described NT antagonist, was found to inhibit selectively and dose-dependently the stimulant effect of NT in the portal vein. The results suggest the existence of specific receptors for NT in the isolated rat portal vein. The response of this tissue to NT, and possibly to other peptides, appears to be dependent upon the presence of a functional PG biosynthetic pathway.     

Postnatal ontogenic development of the adrenergic innervation pattern in the rat portal vein

Summary The postnatal development of the adrenergic innervation pattern in the rat portal vein has been studied with the histochemical fluorescence method of Hillarp and Falck.Stretch preparations and transverse freeze-dried sections of intact portal veins were studied from rats during the first 5 weeks of life and from adult rats. Orientation of undifferentiated smooth muscle cells into two layers was observed at 4 days of age. Dominance of the thick outer longitudinal muscle layer was apparent at two weeks of age. A terminal adrenergic nerve plexus with some varicosities was restricted outside the media at the end of the first week. Ingrowth of penetrating non-terminal adrenergic nerve fibers through the longitudinal muscle layer occurred during the second week of age when the main terminal nerve plexus was developing between the two muscle layers. After 3 weeks of age the adult pattern of a two-dimensional adrenergic plexus between the muscle was established. In the adult rat pharmacological treatment with nialamide and noradrenaline revealed the thin, penetrating non-terminal adrenergic nerve fibers in the longitudinal muscle layer which were poorly visible otherwise.The present observations strongly indicate that the main adrenergic plexus between the two muscle layers emanates directly from the outer axonal plexus. These findings are discussed regarding possible trophic interactions between ingrowing sympathetic adrenergic vasomotor nerves and maturing vascular smooth muscle.Supported by grants from the Swedish Medical Research Council (grants No. 14X-2207, O4P-4173, 3884), Magn. Bergwall's Foundation, G. & M. Lindgren's Foundation, the Medical Faculty of University of Göteborg. The technical assistance of Miss Serney Bööj, Mr. Pär-Anders Larsson and Miss Ann Kjellstedt is gratefully acknowledged     

Further evidence for the purinergic inhibition of adrenergic neurotransmission in the rat portal vein

The inhibition of 3H-noradrenaline (3H-NA) release by adenosine, and the possible involvement of purine receptors in the regulation of transmitter release in the portal vein were studied. The inhibitory effect of different concentrations of adenosine (10, 30, 100 and 300 microM) decreased with frequency of stimulation, but there was no marked concentration-dependence. Tetraethylammonium (TEA) enhanced the 3H-NA overflow induced by transmural stimulation. The adenosine-induced inhibition of 3H-NA overflow was antagonized by TEA. Transmural stimulation induced release of tritium from tissues prelabelled with either 3H-NA or 3H-adenine had a similar pattern of distribution. In contrast, when the rat portal vein was stimulated with (-) NA, the overflow of purine derivates was delayed and the maximum release was achieved 5 min later than the maximum induced by transmural stimulation. Phenoxybenzamine (PBA) increased 3H-NA overflow two-fold, but had no effect on the 3H-purine release induced by transmural stimulation. PBA reduced the 3H-purine release by exogenous (-) NA. These results indicate that in rat portal vein, the purine compounds have pre- and postjunctional origins and that the purine that modulates adrenergic neurotransmission might be of neuronal origin, possibly independent of adrenergic innervation.     

Increased plasma volume in two models of portal hypertension in the rat: cirrhosis of the liver and partial portal vein ligation

Portal hypertension has been studied in the rat to see if it is associated to altered blood volume composition, as it has been shown in other species. Plasma volume was measured by isotope dilution using 99mTc labelled albumin in three groups of male Sprague-Dawley rats: normal rats (controls), partially ligated portal vein rats and rats with Cl4C induced cirrhosis. Plasma volume was significantly higher in rats with portal hypertension due to partially ligated portal vein and cirrhosis than in control animals. Similarly, the calculated blood volume was also significantly higher in the portal hypertensive animals than in control group. Portal hypertension in the rat, therefore, has been demonstrated to be associated to a marked hypervolemia and this finding should be taken into consideration in haemodynamic and pharmacokinetic studies in portal hypertensive rat models.     

Cytoskeletal features in longitudinal and circular smooth muscles during development of the rat portal vein

Immunohistochemistry of -smooth muscle actin and desmin, two markers of smooth muscle cell differentiation, and electron-microscopic observation of thick filaments of myosin were performed on the media of the developing rat hepatic portal vein to gain insights into the chronology of differentiation of its longitudinal and circular smooth muscles. In accordance with the ultrastructural distribution of thin filaments, staining of -smooth muscle actin is lightly positive in the myoblasts at postnatal day 1 and then extends in probably all muscle cells of the developing vessel. Desmin, which appears later than -smooth muscle actin in the two muscles, is distributed throughout the longitudinal layer at day 8, whereas the first arrangements of thick filaments are detectable in most longitudinal muscle cells; at this stage, desmin and thick filaments are absent from the poorly differentiated circular muscle cells. The longitudinal muscle cells differentiate in a strikingly synchronized way from day 8 onwards, conferring a homogeneous structure to the developing and mature longitudinal layer. Several desmin-positive cells and a heterogeneous distribution of thick filaments occur in the circular muscle at day 14; the subsequent extension of these filaments in this layer results in a persisting heterogeneous distribution in the young 7-week-old adult. Many features of the mature smooth muscle cells are established within the third week in the longitudinal muscle, approximately one week before those of the circular layer. These results are consistent with the function of the longitudinal muscle as a spontaneously contractile smooth muscle unit, and emphasize the need for its fast maturation to fulfil its major role in the control of portal blood flow.     

Measurement of pulsatile insulin secretion in the rat: direct sampling from the hepatic portal vein

It has previously been shown that insulin is secreted in discrete secretory bursts by sampling directly from the portal vein in the dog and humans. Deficient pulsatile insulin secretion is the basis for impaired insulin secretion in type 2 diabetes. However, while novel genetically modified disease models of diabetes are being developed in rodents, no validated method for quantifying pulsatile insulin secretion has been established for rodents. To address this we 1) developed a novel rat model with chronically implanted portal vein catheters, 2) established the parameters to permit deconvolution of portal vein insulin concentrations profiles to measure insulin secretion and resolve its pulsatile components, and 3) measured total and pulsatile insulin secretion compared with that in the dog, the species in which this sampling and deconvolution approach was validated for quantifying pulsatile insulin secretion. In rats, portal vein catheter patency and function were maintained for periods up to 2-3 wk with no postoperative complications such as catheter tract infection. Rat portal vein insulin concentration profiles in the fasting state revealed distinct insulin oscillations with a periodicity of approximately 5 min and an amplitude of up to 600 pmol/l, which was remarkably similar to that in the dogs and in humans. Deconvolution analysis of portal vein insulin concentrations revealed that the majority of insulin ( approximately 70%) in the rat is secreted in distinct insulin pulses occurring at approximately 5-min intervals. This model therefore permits direct accurate measurements of pulsatile insulin secretion in a relatively inexpensive animal. With increased introduction of genetically modified rat models will be an important tool in elucidating the underlying mechanisms of impaired pulsatile insulin secretion in diabetes.     

Neural coding and contextual influences in the whisker system

A fundamental problem in neuroscience, to which Prof. Segundo has made seminal contributions, is to understand how action potentials represent events in the external world. The aim of this paper is to review the issue of neural coding in the context of the rodent whiskers, an increasingly popular model system. Key issues we consider are: the role of spike timing; mechanisms of spike timing; decoding and context-dependence. Significant insight has come from the development of rigorous, information theoretic frameworks for tackling these questions, in conjunction with suitably designed experiments. We review both the theory and experimental studies. In contrast to the classical view that neurons are noisy and unreliable, it is becoming clear that many neurons in the subcortical whisker pathway are remarkably reliable and, by virtue of spike timing with millisecond-precision, have high bandwidth for conveying sensory information. In this way, even small (~200 neuron) subcortical modules are able to support the sensory processing underlying sophisticated whisker-dependent behaviours. Future work on neural coding in cortex will need to consider new findings that responses are highly dependent on context, including behavioural and internal states. This article is part of a special issue on Neuronal Dynamics of Sensory Coding.     

Potential role of the neuropeptide CGRP in the induction of differentiation of rat hepatic portal vein wall

The media of the rat hepatic portal vein is composed of an internal circular muscular layer (CL) and an external longitudinal muscular layer (LL). These two perpendicular layers differentiate progressively from mesenchymal cells within the first month after birth. In this paper, we studied the development of calcitonin gene-related peptide (CGRP) innervation during post-natal differentiation of the vessel. We show that CGRP innervation is already present around the vessel at birth in the future adventitia but far from the lumen of the vessel. Progressively, CGRP immunoreactive fibers reached first LL then CL. CL by itself become only innervated at day 14 after birth. This corresponds to the time at which thick filaments (myosin) are visible in electron microscopy and desmin visualisable by immunocytochemistry. Furthermore, we provide evidence by autoradiography, that binding sites for CGRP are transiently expressed on the portal vein media at day 1 and 14 after birth. Vascular smooth muscle cells were transfected with constructs containing promoters for desmin or smooth muscle myosin heavy chain (smMHC). CGRP treatment of the cells significantly increased the expression of smMHC. Overall these results suggest that CGRP can potentially influence the differentiation of smooth muscle cells from the vessel wall.     

门静脉海绵样变大鼠门静脉氧化应激损伤的研究

目的:考察门静脉海绵样变性(CTPV,Cavernous transformation of portal vein)大鼠体内氧化应激的状态以及氧化应激对门静脉结构的影响。方法:采用门脉部分结扎法复制CTPV大鼠动物模型;通过测定门静脉内血浆超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活力来分析机体抗氧化能力,测定丙二醛(MDA)含量分析机体氧化能力;门静脉HE染色观察门静脉病理变化。结果:Sham组大鼠门静脉造影显示门静脉通畅,无曲张与扩张;门静脉病理学检查显示门静脉管腔无增大、内皮细胞光滑、中膜平滑肌层无增厚、外膜完整。CTPV组大鼠门静脉造影显示门静脉周围侧支循环形成,门静脉病理检查显示多个管腔大小不一、外形不规则血管腔,管腔之间为较狭窄的纤维性间隔,其内可见脂肪细胞、散在的淋巴细胞及肥大细胞等,门静脉管腔增大、血管内膜受损、内皮细胞脱落、中膜平滑肌增厚和血栓形成。与Sham组大鼠比较,CTPV组大鼠SOD、GSH-Px活性降低(93.79+8.87μU/L Vs103.05+8.07μU/L,P<0.05,157.44+26.46U/ml Vs709.09+83.21U/ml,P<0...     

Neural and Pavlovian influences on immunity

The traditional view that the nervous and immune systems are functionally independent (aside from general stress effects and autoimmune disorders of the nervous system) is being challenged by a new view that the nervous system regulates the activity of the immune system. If this is true, it should be possible to change the activity of the immune system by means of Pavlovian conditioning, just as it is possible to condition other physiological events influenced by the autonomic nervous system or neuroendocrine substances. Evidence for autonomic and neuroendocrine modulation of immune activity is briefly reviewed; and, the various studies reporting conditioned immune effects, the physiological mechanisms most likely involved, and their possible significance are discussed.