Trophic effect of the sympathetic nervous system on vascular smooth muscle

While the vasomotor effect of the sympathetic nervous system (SNS) on the arterial wall is well recognized, its trophic function is not. It is the aim of these studies to demonstrate this all-important function as it relates to the vascular muscle. Although the exact mechanism by which sympathetic nerve impulses influence the metabolism of the vessel wall is unknown, effects of sympathectomy can be demonstrated. Several lines of evidence indicate that chronic absence of sympathetic innervation in rabbits increases collagen synthesis and decreases activity of tricarboxylic acid cycle enzymes in the vascular wall. When chemically sympathectomized rabbits were fed a 1% cholesterol dietary supplement for 80 days, the aortas of these rabbits contained significantly more cholesterol and total lipids than those from fully innervated controls in spite of insignificant differences in plasma lipids. In a subsequent series of experiments we analyzed the efficacy of the SNS in two strains of pigeons. White Carneau (WC) pigeons are known by their susceptibility to atherosclerosis of the aorta while Show Racer (SR) pigeons are not. Our results demonstrate that the abdominal aorta of WC pigeons has less sympathetic innervation and it declines faster with age than that of SR pigeons. The results of the described studies documenting the direct trophic influence of the SNS on the arterial wall are reinforced by the similarity to the vessel wall changes induced by partial sympathectomy and natural aging. Various phases of this work were done in collaboration with Drs. N. Alexander, D. Amiel, C.M. Bloor, M. Chvapil, J.D. Turner and T. Zemplenyi.     

Low-frequency noise effects on the rat parotid gland: A transmission electron microscopy study

Introduction: Low-frequency noise (LFN) is a ubiquitous physical stressor known to cause degenerative cellular changes and organ alterations with functional repercussions both in humans and animals. Materials and methods: After acceptance of the study protocol by a local ethics committee, 20 Wistar rats were randomly divided into two equal groups. One group was kept in silence and the other continuously exposed to LFN during 13 weeks. The rats had unlimited access to water and were fed standard rat chow. After exposure, the animals were sacrificed and the parotid glands were excised and prepared for transmission electron microscopy. Results: The acinar cells showed marked ultrastructural alterations, such as intracellular vacuolization, loss of cell polarity, increased heterochromatin, cytoplasmic inclusions, and oncocytic transformation. Conclusions: LFN induces ultrastructural changes in the rat parotid gland that correlate with previously described functional changes.     

An ultrastructural study of oncocytoma and oncocytic carcinoma of the parotid gland

One case of oncocytoma and another of oncocytic carcinoma of the parotid gland are reported with ultrastructural studies. The incidence of oncocytoma varies from 0.1% to 1.4% of all parotid gland tumors, while oncocytic carcinoma is extremely rate. The oncocytoma was composed of polyhedral cells with fine eosinophilic granular cytoplasm and a rounded nucleus. The tumor cell clusters were surrounded by basement membrane. The tumor cells of the oncocytic carcinoma were also characterized by eosinophilic cytoplasm, but cellular atypia and mitotic figures were found. Electron microscopically, the cytoplasm of the oncocytoma was packed with abundant mitochondria. They were oval or elongated in shape with stacked cristae. Although the tumor cells of the oncocytic carcinoma also contained many mitochondria, their number was less than that of the benign case, and stacked cristae were very few. Basement membrane was not seen. The ultrastructural characteristics of oncocytoma and oncocytic carcinoma of the parotid gland are discussed with reference to previous reports.     

Fluoride stimulation of the rat parathyroid gland: An ultrastructural study

The parathyroid glands of rats given 150 ppm fluoride in the drinking water for 10 weeks are evaluated ultrastructurally and compared to the parathyroid glands of untreated rats. As a result of fluoride ingestion, the majority of the parathyroid cells are dark chief cells, indicating that these cells are in the active stages of the secretory cycle. More significantly, in the fluoride-treated rats, the cytoplasmic organelles of the dark chief cells are even more developed that those seen in the dark chief cells of untreated rats. The dark cells contain an electron-dense cytoplasm with abundant lamellar arrays of rough endoplasmic reticulum, spiral aggregations of free ribosomes, multiple dilated Golgi complexes, and increased numbers of secretory granules. The cells are at a minimum dimension with maximum tortuosity of the plasma membranes; and, as a result, large intercellular spaces are often seen between contiguous cells. Based on these observations, it is suggested that, in the fluoride-treated rat, a type of secondary hyperparathyroidism develops resulting in an increase in the organelles involved in protein synthesis and secretion.     

Benign lymphoepithelial cysts of the parotid gland. A histologic, cytologic, and ultrastructural study

Five cases of benign lymphoepithelial cysts (BLCs) of the parotid gland are reported, and the histologic, aspiration cytologic, and ultrastructural findings are described in detail. These uncommon parotid lesions contain epithelium-lined cystic spaces encased by abundant lymphoid tissue with germinal centers. The epithelium was "mucoepidermoid" in three of our cases and squamous in two. Familiarity with the morphologic features of BLCs should make it possible to distinguish them from similar-appearing cystic lesions, especially low-grade cystic mucoepidermoid carcinoma and cystic types of benign lymphoepithelial lesion (so-called Mikulicz's disease). These distinctions, however, are difficult on aspiration cytology specimens.     

Postnatal development of the duct system in the mouse parotid gland

The morphology of the parotid gland in adult mice is mouse strain-specific. C57BL/6 and C3H/He strains of mouse are representatives of two types of the morphology identified previously. The postnatal development of such morphologic differences was investigated by sialography of excised glands of these strains of mouse. It was observed that the mouse strain-dependent morphological characteristics were already present at birth, except for the branching pattern of the peripheral duct system, which became differentiated at 3 weeks of age. These results indicate that the C3H/He mouse-specific branching pattern of the peripheral ducts reflects the profile of matured secretory units and ducts, and that the C57BL/6 mouse-specific pattern resembles that of an immature C3H/He mouse.     

Effects of streptozotocin-induced diabetes on the rat parotid gland

The structure of the rat parotid gland was studied in male rats from 4 hours up to 1 year after induction of diabetes by the administration of streptozotocin (STZ, 65 mg/kg). Blood glucose and triglyceride levels were markedly increased, and plasma insulin levels were significantly decreased within 24 hours after STZ. The earliest detectable alteration in acinar cell structure was the presence of small lipid droplets in the basal cytoplasm at 24 hours. Lipid accumulation continued, reaching a peak at 4.5 months after STZ, when the acinar cells contained large lipid vacuoles. By 1 week the Golgi apparatus was enlarged and GERL was prominent at the trans Golgi face. Membrane-bound cytoplasmic crystalloids occurred in acinar cells 1 month after STZ administration and were numerous in older animals (10 to 12 months). These crystalloids occasionally were reactive for trimetaphosphatase, a cytochemical marker for lysosomes. Similar crystalloids as well as large, dense, phagosome-like bodies were also present in the striated duct cells. Macrophages containing acinar cell debris and crystalloids were frequently observed, often in association with the intercalated ducts. Focal alterations in the basement membranes, consisting of multiple layers, loops, and amorphous patches, and "redundant" folds, occurred as early as 2 months and were relatively frequent 10 to 12 months after STZ administration. These results suggest that maintenance of the normal structure and function of the rat parotid gland may, in part, be insulin dependent.     

Neuroendocrine carcinoma of the parotid gland: A report of two cases with ultrastructural and immunohistochemical studies

Two cases of primary small cell carcinoma of the parotid gland are reported. This rare neoplasm usually presents as a painful or painless mass in the gland. The finding of neurosecretory granules by electron microscopic study, combined with strong immunoreactivity for neuron-specific enolase and chromogranin, confirms the true neuroendocrine origin of the carcinoma. This tumor appears to have a better prognosis than small cell carcinoma of the lung, which it resembles histologically.     

Regeneration of the parotid gland in the rat

Summary Parotid gland regeneration was studied in rats in which all of the left gland and part (50–60%) of the right had been removed. In young rats weighing 60–100 g, regeneration occurred in 19% of cases, as judged by the restoration of the weight of the organ. The weight of the glands did not always reach the initial level, however, and averaged 80% of the weight in control animals.The number of cases with gland regeneration increased in adult rats when the capsule was left open after the operation. Histological investigation showed that regeneration does not occur by growth starting at the injured surface, but rather by the proliferation of the secretory epithelium (regenerative hypertrophy) of the acini over the whole organ.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 50, No. 10, pp. 113–118, October, 1960     

Micro-anatomy of the renal sympathetic nervous system: a human postmortem histologic study

Hypertension remains an epidemic uncontrolled with pharmacologic therapies. A novel catheter inserted into the renal artery has been shown to lower blood pressure by ablating the renal sympathetic nerves with radiofrequency energy delivered through the arterial wall. We report a histologic study describing the anatomic substrate for this technique, specifically the renal sympathetic nervous system. Histological sections from proximal, middle, and distal renal artery segments from nine renal arteries (five human autopsies) were analyzed. Nerves were manually counted and their distance from the lumen-intima interface was measured using a micrometer. The nerves were then categorized by location into 0.5-mm-wide "rings" that were arranged circumferentially around the renal artery lumen. Of all nerves detected, 1.0% was in the 0-0.5 mm ring, 48.3% were in the 0.5-1.0 mm ring, 25.6% were in the 1.0-1.5 mm ring, 15.5% were in the 1.5-2.0 mm ring, and 9.5% were in the 2.0-2.5 mm ring. Beyond 0.5 mm, the proportion of nerves tended to decrease as the distance from the lumen increased. Totally, 90.5% of all nerves in this study existed within 2.0 mm of the renal artery lumen. Additionally, the number of nerves tended to increase along the length of the artery from proximal to distal segments (proximal = 216; middle = 323; distal = 417). In conclusion, our analysis indicates that a great proportion of renal sympathetic nerves have close proximity to the lumen-intima interface and should thus be accessible via renal artery interventional approaches such as catheter ablation. This data provides important anatomic information for the development of ablation and other type devices for renal sympathetic denervation.     

A sympathetic view of the sympathetic nervous system and human blood pressure regulation

New ideas about the relative importance of the autonomic nervous system (and especially its sympathetic arm) in long-term blood pressure regulation are emerging. It is well known that mean arterial blood pressure is normally regulated in a fairly narrow range at rest and that blood pressure is also able to rise and fall 'appropriately' to meet the demands of various forms of mental, emotional and physical stress. By contrast, blood pressure varies widely when the autonomic nervous system is absent or when key mechanisms that govern it are destroyed. However, 24 h mean arterial pressure is still surprisingly normal under these conditions. Thus, the dominant idea has been that the kidney is the main long-term regulator of blood pressure and the autonomic nervous system is important in short-term regulation. However, this 'renocentric' scheme can be challenged by observations in humans showing that there is a high degree of individual variability in elements of the autonomic nervous system. Along these lines, the level of sympathetic outflow, the adrenergic responsiveness of blood vessels and individual haemodynamic patterns appear to exist in a complex, but appropriate, balance in normotension. Furthermore, evidence from animals and humans has now clearly shown that the sympathetic nervous system can play an important role in longer term blood pressure regulation in both normotension and hypertension. Finally, humans with high baseline sympathetic traffic might be at increased risk for hypertension if the 'balance' among factors deteriorates or is lost. In this context, the goal of this review is to encourage a comprehensive rethinking of the complexities related to long-term blood pressure regulation in humans and promote finer appreciation of physiological relationships among the autonomic nervous system, vascular function, ageing, metabolism and blood pressure.     

Sensitization of the rat parotid gland to secretagogues following either parasympathetic denervation or sympathetic denervation or decentralization

The sensitivity of the rat parotid gland to chemical agents was examined 2–3 weeks after either parasympathetic denervation or sympathetic denervation or decentralization. The parasympathetically denervated gland was markedly sensitized towards methacholine; a nonspecific supersensitivity mainly mediated via α-adrenoceptors was also demonstrated. The sympathetically denervated gland had developed a supersensitivity which was both of the pre-and the postjunctional type; it was predominantly of the former type to noradrena-line and adrenaline, and entirely so to phenylephrine; it was of the latter type to isoprene-line, and also to methacholine. The sympathetically decentralized gland was mainly sensitized towards noradrenaline, adrenaline and isoprenaline. The postjunctional super-sensitivity developed towards the sympathomimetic drugs after sympathetic decentralization was of about the same magnitude as that observed after sympathetic denervation; this type of supersensitivity was mainly mediated via β-adrenoceptors.     

The effect of calmodulin antagonists on amylase release from the rat parotid gland in vitro

The effect of several calmodulin antagonists on the release of alpha-amylase (EC 3.2.1.1) from rat parotid gland minces was investigated as an approach to determine whether calmodulin has a role in the stimulus-secretion coupling mechanism in this tissue. The phenothiazines, trifluoperazine, chlorpromazine, and thioridazine, failed to inhibit amylase release induced by N6,O2'-dibutyryl adenosine 3':5'-cyclic monophosphate. All three phenothiazines increased basal amylase release at high concentrations. This release was independent of cellular energy, indicating that the release was probably due to the membrane perturbing properties of these compounds rather than their ability to antagonize calmodulin. R24571, a more potent calmodulin antagonist, also failed to inhibit amylase release induced by N6,O2'-dibutyryl adenosine 3':5'-cyclic monophosphate but increased basal amylase release. A different calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, partially inhibited release while 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) completely blocked the amylase release induced by the cyclic AMP derivative. However, concentrations of TMB-8 inhibiting amylase release drastically reduced the ATP concentration of rat parotid minces, suggesting that the inhibition of secretion was due to toxic effects of TMB-8 on parotid cells rather than the ability of the compound to antagonize calmodulin. The use of calmodulin antagonists has therefore failed to implicate calmodulin as an intermediate in the stimulus-secretion coupling mechanism of the rat parotid gland.