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Quantitative autoradiographic characterization of receptors for angiotensin II and other neuropeptides in individual brain nuclei and peripheral tissues from single rats.

Autoradiographic techniques coupled with computerized microdensitometry and comparison with 125I standards were used to characterize and quantitate receptors for neuropeptides in rat brain and adrenal and pituitary glands. These techniques are rapidly performed, anatomically precise, and more sensitive than membrane binding techniques. They permit the determination of complete saturation curves and Scatchard analysis in discrete nuclei of the rat brain and in single rat pituitary and adrenal glands. Angiotensin II (AII) receptors were quantitated after incubation of 16-micron tissue sections with the AII agonist 125I-[Sar1]-AII. High-affinity, high-density AII receptors were present in the organon subfornicalis, organon vasculosum laminae terminalis and nuclei triangularis septalis, suprachiasmatis, and paraventricularis of the rat and in rat adrenal capsule-zona glomerulosa area, adrenal medulla, and anterior pituitary. These techniques could be used for precise localization and quantitation of other neuropeptide receptors in single rat brain nuclei, after optimizing the assay conditions and provided that suitable 125I ligands are available.

Adrenal Cortex↗

Regional blood flow in brain and peripheral tissues during acute experimental arterial subdural bleeding.

The effects of a large intracranial arterial subdural bleeding on regional blood flow in the brain (rCBF) and in other body organs were studied, using a porcine model. The bleeding was produced by leading blood through a catheter from the abdominal aorta via an electronic drop recorder into the subdural compartment (SDC) over the left cerebral hemisphere. Pressures in the right lateral cerebral ventricle and in the cisterna magna were recorded along with 15 other vital parameters. Measurements of rCBF were carried out using radioactive microspheres 1) before the start of bleeding, 2) during the early bleeding phase, and 3) during the late bleeding phase. When the bleeding was initiated, the intracranial pressures rose within one minute to a level approximately 40 mmHg below the systemic arterial pressure, whilst the latter usually decreased 30-40 mmHg. In the subsequent early bleeding phase the cerebral perfusion pressure and the bleeding pressure fluctuated at a level of approximately 40 mmHg for several minutes. In the late bleeding phase, the perfusion pressure decreased maximally, even when a Cushing reaction was activated. During the early bleeding phase the changes in rCBF varied between the cerebral regions. However, the mean flow remained largely constant in the presence of a decreasing cerebrovascular resistance, indicating that autoregulation of CBF was intact. Concomitantly, cardiac output and heart rate decreased, whilst regional blood flow in extracerebral organs tended to increase, possibly due to an intracranial effect on the autonomic nervous system. In the late bleeding phase, rCBF was critically reduced in all regions, in spite of a marked rise in systemic arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Assessment of the perfusion in peripheral tissue beds by subcutaneous oximetry and gastric intramucosal pH-metry in elective colorectal surgery.

Gastric intramucosal pH (pHi) and subcutaneous oxygen tension (PscO2) were compared with traditional perfusion parameters in patients undergoing elective colorectal surgery and were related to clinical outcome. Ten patients were studied per- and postoperatively and tissue oximetry studies were also performed in a group of 10 healthy volunteers. The response of PSCO2 to oxygen breathing proved to be the most sensitive predictor of clinical outcome. Of the 10 patients 8 failed to respond to an O2 challenge, while all 10 volunteers in the control group did so. Out of those 8 patients 6 presented with mainly infectious complications while only 3 had an inadequate perioperative urine output and none presented with signs of arterial or of gastric intramural acidosis. The present study suggests a possible relationship between clinical outcome and oxymetric signs of tissue hypoperfusion after O2 challenge in surgical patients, even in the presence of an adequate urine output and a normal gastric wall pH.

Adult↗

Steroid hormones and the cardiovascular system: direct actions of estradiol, progesterone, testosterone, gluco- and mineralcorticoids, and soltriol [vitamin D] on central nervous regulatory and peripheral tissues.

Knowledge of steroid hormone sites of action and related effects in cardiovascular and neural regulatory tissues is reviewed. Evidence for nuclear receptor sites is derived mainly from autoradiographic studies with relatively intact tissues and some biochemical studies with tissue homogenates. In the heart and in the walls of blood vessels, estradiol, dihydrotestosterone, corticosterone, aldosterone, dexamethasone, and soltriol (vitamin D) show nuclear binding. In the brain and spinal cord, neuronal regions associated with cardiovascular regulation contain nuclear receptors in specific patterns for each steroid hormones, including progesterone and soltriol. These data indicate that all steroid hormones exert direct actions on the cardiovascular system at its different levels of organization, thus enabling adjustment to the changing demands during reproduction (gonadal steroids), stress (adrenal steroids), and solar seasons (vitamin D-soltriol).

Adrenal Cortex Hormones↗

Calcitonin receptor-like receptor: identification and distribution in human peripheral tissues.

We report here on the characterization and immunohistochemical localization in human tissues of calcitonin receptor-like receptor (CRLR) which was recently found to mediate the effects of both calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM). Western blot analysis using antibodies raised against the first extracellular loop and the carboxy-terminal part of hCRLR, respectively, detected two major bands corresponding to about 70 and 60 kDa in membrane preparations of cultured endothelial cells and numerous organs including lung, heart ventricle and kidney. Immunohistochemical analysis of the cardiovascular system revealed CRLR-like immunoreactivity (CRLR-LI) in the endothelium of all blood vessels including large and small arteries, veins and capillaries, and in heart muscle cells and endocardium. The lung showed intense staining over the alveolar capillaries. Within the digestive tract, staining was observed over the cells lining the excretory ducts of the parotid gland, over the epithelium of the fundic glands of stomach, endocrine cells of the duodenum and ileum and some myenteric ganglia. The kidney presented staining of the juxtaglomerular arteries, the glomerular capillaries and chief cells of the collecting duct. Within the endocrine organs, a strong CRLR-LI signal was observed over the Langerhans islets, and weak immunoreactivity in the Leydig cells of testis. Spleen showed intense staining in trabecular veins and sinuses. Macrophages displayed a variable immunoreactivity. Our data demonstrate a wide distribution of CRLR throughout the human body and suggest CRLR to be involved in the mediation of a variety of actions in addition to vascular control.

Adrenomedullin↗

Cell-specific localization of the sulphydryl oxidase QSOX in rat peripheral tissues.

Rat quiescin/sulphydryl oxidase (rQSOX) introduces disulphide bridges into peptides and proteins with the reduction of molecular oxygen to hydrogen peroxide. Its occurrence has been previously highlighted in a wide range of organs by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analyses, methods that have provided information concerning its expression in whole organs but that do not reveal the cell types expressing this enzyme. In this report, in addition to RT-PCR and Western blot experiments, the cell-specific localization of rQSOX has been investigated in a wide range of male and female adult rat tissues by using in situ hybridization and immunohistochemistry. Labelling was detected in most organs and systems including the immune, endocrine and reproductive systems, the respiratory, digestive and urinary tracts and the skin. No labelling was observed in the heart, blood vessel endothelium, liver or smooth and skeletal muscles. rQSOX expression was mainly localized in epithelial cells specialized in secretion, strengthening the hypothesis that QSOX enzymes play an important role in the mechanism of secretion, notably in the folding of secreted proteins. The intracellular patterns of immunolabelling indicate that the protein usually follows the secretory pathway, which is in accordance with its secreted nature and its presumed involvement in the elaboration of the extracellular matrix. In seminiferous tubules, where a high level of expression was noticed, QSOX might play an important physiological role in sperm function and serve as a marker for the diagnosis of male infertility.

Animals↗