Acta physiologica Scandinavica. Supplementum最新文献

{"title":"Airborne nitric oxide: inflammatory marker and aerocrine messenger in man.","authors":"J O Lundberg","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>1. In healthy subjects, exhaled NO originates mainly from the upper airways with only a minor contribution from the lower airways and the lungs. A large NO production takes place in the epithelium of the paranasal sinuses and this NO contributes considerably to the levels of NO found in nasally exhaled air. Immunohistochemical and mRNA in situ hybridisation studies suggest that sinus NO synthase is identical or very closely related to the human iNOS. Furthermore, the NOS activity in sinus mucosa is mostly Ca(2+)-independent. However, the regulation of sinus NOS expression seems to differ fundamentally from what has earlier been described for iNOS. Thus, sinus NOS is constitutively expressed and seems resistant to steroids. The high local NO concentrations in the nasal airways and the sinuses may help to protect against airborne infectious agents. Thus, airborne NO may represent the very first line of defence in the airways, possibly acting on pathogens even before they reach the mucosa. 2. Nasal concentrations of NO are markedly reduced in children with Kartagener's syndrome and in patients with CF. A simple chemiluminescence test test could be of help in early non-invasive diagnosis of these chronic airway diseases. 3. Inhaled endogenous NO, derived from the upper airways, may be involved in regulation of pulmonary function in man. NO will reach the lower airways and the lungs with the inspired air and at levels that are especially high during nasal breathing. This NO may act by enhancing blood flow preferentially in well ventilated areas of the lung, thus optimizing ventilation/perfusion matching. The involvement of autogenous NO in regulation of pulmonary function may represent a novel physiological principle, namely that of an enzymatically produced airborne messenger. The term \"aerocrine\" may be appropriate for this action of NO in the airways. These findings may also help to explain one biological role of the enigmatic human paranasal sinuses, the major sources of NO in the upper airways. 4. A continuous production of NO takes place in the acidic stomach through chemical reduction of nitrite present in swallowed saliva. This is the first evidence of non-enzymatic NO production in humans. Stomach NO may be involved in local defence against swallowed pathogens and in regulation of superficial mucosal blood flow and mucus production. 5. Luminal concentrations of NO are increased in the lower airways of asthmatic children, in the colon of patients with inflammatory bowel disease, and in the urinary bladder of patients with cystitis. Local steroid treatment reduces orally exhaled NO levels in asthmatic children. Nasal NO levels did not differ between controls and asthmatic children with or without concomitant allergic rhinitis. In conclusion, nitric oxide found in exhaled air originates mainly in the upper airways. A large production of NO takes place in the paranasal sinuses from a constitutively-expressed, steroid-resistant \"inducible-li","PeriodicalId":75414,"journal":{"name":"Acta physiologica Scandinavica. Supplementum","volume":"633 ","pages":"1-27"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19842352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative sensory examination of epidural anaesthesia and analgesia in man.","authors":"J Brennum","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75414,"journal":{"name":"Acta physiologica Scandinavica. Supplementum","volume":"634 ","pages":"1-27"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19842353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensory neuropeptides and nitric oxide in nasal vascular regulation.","authors":"J Rinder","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>1. RR may act as a preferential capsaicin antagonist in the pig nasal mucosa in vivo. However, the present data reveal a narrow concentration range for the selective actions of RR. Moreover, RR has systemic cardiovascular side effects despite local i.a. infusion in the IMA. 2. Acoustic rhinometry is a useful method for investigations of changes in nasal cavity volume in the pig in vivo. 3. The NK1-receptor antagonist RP-67,580 lacks NK1-receptor blocking properties in the pig in vivo. In contrast, CP-96,345 and SR 140.333 significantly blocked SP-mediated vascular effects in the pig nasal mucosa and superficial skin, indicating species dependent NK1-receptor selectivity. Capsaicin-induced vasodilatation in the IMA was not attenuated after administration of CP-96,345 and SR 140.333 whereas the superficial blood flow in the nasal mucosa and skin was slightly reduced. The CGRP-receptor antagonist hCGRP 8-37 markedly reduced the capsaicin-evoked vascular effects in the pig nasal mucosa and superficial skin. 4. Vanilloid receptors, as revealed by 3H-RTX binding, are present in the pig nasal mucosa although with different characteristics compared to vanilloid receptors in the pig dorsal horn. Capsaicin, RTX and LA evoked vasodilatation in the pig nasal mucosa in a similar fashion, indicating activation of sensory nerves. The LA (proton)-evoked vasodilatation was significantly attenuated after local i.a. infusion of hCGRP 8-37, closely resembling the results obtained from the capsaicin challenge before and after CGRP-receptor blockade. Capsazepine did not reduce the capsaicin-and LA-evoked vasodilation in the pig nasal mucosa. This agrees well with the observation that capsazepine did not inhibit RTX binding to vanilloid receptors in pig nasal mucosal membranes. 5. Capsaicin desensitisation of the human nasal mucosa attenuated the subjective pain response as well as the reduction of the cross-sectional area in the nasal cavity evoked by LA and hypertonic saline. This finding gives further support to the hypothesis that protons may act as endogenous ligands to the vanilloid receptor also in man. 6. Systemic administration of the NOS inhibitor L-NNA significantly reduced basal nasal V Con and increased C Vol in the pig. The effects evoked by L-NNA were similar in magnitude to those of phenylephrine and UK 14304, although of much longer duration. Administration of L-NNA did not reduce the vasodilator responses to SP and ACh, suggesting that these substances may mediate their vascular effects via one or several other mechanisms beside the NO/cGMP pathway. Moreover, capsaicin-, VIP-, and nitroprusside-evoked vasodilatation was not reduced after NOS inhibition. 7. Heavy physical exercise and alpha-adrenoceptor agonists reduce nasal cavity NO levels acutely in man. This may be due to a reduced supply of substrates for NO synthesis in the paranasal sinus epithelium, the primary NO production site in the upper airways. However, prolonged use of the alpha 2","PeriodicalId":75414,"journal":{"name":"Acta physiologica Scandinavica. Supplementum","volume":"632 ","pages":"1-45"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19772218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro studies of human skeletal muscle: hormonal and metabolic regulation of glucose transport.","authors":"J R Zierath","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75414,"journal":{"name":"Acta physiologica Scandinavica. Supplementum","volume":"626 ","pages":"1-96"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19507531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allergen-induced late airways reactions in the pig. Influence of endogenous and exogenous glucocorticoids.","authors":"C Fornhem","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75414,"journal":{"name":"Acta physiologica Scandinavica. Supplementum","volume":"631 ","pages":"1-48"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19692295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroendocrine mechanisms during reversible hypovolaemic shock in humans with emphasis on the histaminergic and serotonergic system.","authors":"S H Matzen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In humans, the head-up tilted position results in central hypovolaemia which mimicks haemorrhage and is associated with cardiovascular changes that can be divided into two stages. 1) One stage with increase in HR and vascular resistance and a slight increase in MAP. 2) Another stage with decrease in HR, vascular resistance and MAP and appearance of presyncopal symptoms (hypovolaemic shock). The first stage is \"sympathoexcitatory\" as plasma NA originating from postganglionic vasoconstrictory sympathetic neurons increase. Limb vascular resistance contributes to the increase in TPR at this time. The second stage is \"sympathoinhibitory\" in nature as plasma NA slightly decreases, or remains unchanged, while plasma A, originating from the adrenal medulla, raises. This pattern is a reflection of a differentiated sympathetic response as an increase in the activity of the nerves innervating the adrenals and decrease in renal sympathetic nerves has been reported by others. There is a decrease in limb as well as total vascular resistance. The secretion of potent vasoactive peptides may contribute to the circulatory changes taken place during head-up tilt. The head-up tilted position is associated with central hypovolaemia which is reliably monitored by electrical impedance. There is a close relation between the increase in thoracic electrical impedance and the decrease in plasma ANP which is regulated by atrial stretch. Also, from recording of technetium labeled red blood cells and measurements of haematocrite the decrease in CBV is reflected by thoracic electrical impedance. In contrast, CVP reflects changes in CBV during the initial head-up tilt only, whereafter CVP usually is unchanged or may even increase. After the initial head-up tilt the decrease in the CBV is caused by further reduction in plasma volume as shown by increase in haematocrite and unchanged distribution of labeled red blood cells. This mechanism is reflected by application of regional electrical impedance measurements at a low and high frequency current. The low frequency current, passing extracellular fluid only, changing more than the high frequency current that passes extra as well as intracellular fluid. Central hypovolaemia was found to stimulate the pituitary-adrenal axis, and the development of hypotension strongly increases plasma ACTH, beta-END, cortisol and PRL. Blocking histaminergic receptors did not change the pituitary-adrenal response to central hypovolaemia, while the sympathoadrenal response was affected by histaminergic receptor blockade. The H2-receptor antagonist cimetidine inhibited plasma A, while the H1-receptor antagonist mepyramine attenuated plasma NA and reduced cardiovascular tolerance, and also induced some sedation. A possible effect of sedation and anxiolysis was investigated by administration of the GABAergic drug diazepam. This drug did not change the cardiovascular response to head-up tilt, but reduced the increase in plasma cortisol. This indicat","PeriodicalId":75414,"journal":{"name":"Acta physiologica Scandinavica. Supplementum","volume":"628 ","pages":"1-31"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19773515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticosteroid metabolism in isolated perfused rat liver and kidney. Experimental studies with emphasis on aldosterone.","authors":"M Egfjord","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The metabolism of corticosteroids, especially of aldosterone, the most important mineralocorticoid, and of prednisone, a synthetic glucocorticoid, was studied in the isolated perfused liver (IPL) and in the isolated perfused kidney (IPK) of the rat. In IPL, the elimination of aldosterone at 10(-9)-10(-6) M exhibited first order kinetics. Aldosterone was converted to tetrahydroaldosterone (THA), and dihydroaldosterone (DHA) (reduced metabolites), a metabolite less polar than THA, and predominantly to more polar metabolites. These consisted of conjugated reduced metabolites, and of greater amounts of unconjugated polar metabolites. Aldosterone metabolite accumulated rapidly in the circulation. Only the polar metabolites were later excreted in the bile. The elimination of prednisone at 10(-6) M also exhibited first order kinetics, but the clearance of aldosterone was 80% higher than the clearance of prednisone, indicating that different hepatic enzymes are involved in the metabolism of these corticosteroids. In IPK, the clearance of aldosterone was only about 2% of the hepatic clearance, and amounted to 39% of the renal glomerular filtration rate. The excretory and metabolic clearance in the kidney amounted to 26% and 74%, respectively. In the combined isolated perfused liver and kidney (CIPLK) hepatic polar, both unconjugated and conjugated reduced, and less polar reduced, aldosterone metabolites accumulated in the perfusate. Only polar metabolites were excreted in bile, while all circulating metabolites were isolated from urine within 90 minutes. This indicated, that the aldosterone metabolites, which are found in the kidney are formed predominantly in the liver. The presence of the kidney in the perfusion circuit seemed to inhibit the hepatic metabolism of aldosterone, as the total clearance of aldosterone in CIPLK was 23% lower than in the single perfused liver. Furthermore, addition of aldosterone 10(-9) M to CIPLK, but not to IPK without a liver, resulted in an increasing kaliuresis in 3 subsequent periods of 30 minutes, without any concomitant antinatriuresis. The hepatic aldosterone metabolites, which were released to the perfusate in the combined experiments, thus, seemed to possess kaliuretic effect. The metabolism of aldosterone in IPL was sex dependent. In female rat liver a 75% higher clearance of aldosterone per gram of liver was found, compared to that of male rat liver obtained from rats with a similar age. And the total hepatic clearance of aldosterone was 33% higher in female rats than in younger male rats with a similar body weight. The formation of free and conjugated THA and DHA was only observed in male rat liver, while a metabolite less polar than THA was only observed in female rat liver. The predominating polar metabolites in female rat liver consisted of at least 3 polar peaks, which were neither glucuronides nor sulfates of reduced less polar aldosterone metabolites. The sex dependence of the hepatic metabolism of al","PeriodicalId":75414,"journal":{"name":"Acta physiologica Scandinavica. Supplementum","volume":"627 ","pages":"1-42"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19816185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoradiographic visualization and pharmacological characterization of vanilloid (capsaicin) receptors in several species, including man.","authors":"A Szallasi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Sensory neurons sensitive to vanilloids (the paradigm of which is capsaicin, the pungent principle in hot peppers) were visualized by [3H]resiniferatoxin (RTX) autoradiography in several species, including man. Vanilloid binding sites were detected in somatic (trigeminal and dorsal root) and visceral (nodose) sensory ganglia, peripheral (vagal and sciatic) nerves, dorsal horn of the spinal cord, as well as in nuclei in the central nervous system receiving sensory input, such as the nucleus of the solitary tract (containing vagal afferents) and the spinal trigeminal nucleus. Twenty four hrs after ligation of the vagal or the sciatic nerves, a strong accumulation of specific RTX binding sites was observed proximal to the ligature, implying anterograde intraaxonal receptor transport from the nodose and dorsal root ganglia, respectively, to the periphery. RTX induced a dose-dependent loss of vanilloid receptors in the spinal cord and urinary bladder of the rat which was entirely due to a reduction in Bmax. This receptor loss was reversible in the bladder, where the recovery of the binding was accompanied by a restoration of the neurogenic plasma extravasation response, but was irreversible in the spinal cord. These findings suggest that vanilloid receptor loss after RTX treatment can be either reversible (desensitization) or irreversible (most likely reflecting neurotoxicity). Comparably high levels of specific RTX binding were found in human, guinea pig and rat bronchi (species known to respond to vanilloids differently), suggesting that vanilloid receptors can mediate distinct patterns of biological activities among species. Of the species examined, none showed a close resemblance in RTX binding parameters to human vanilloid receptors in spinal cord. The vanilloid receptor antagonist capsazepine was shown to inhibit RTX binding consistent with a competitive mechanism. Both inter- and intraspecies heterogeneity was observed in the affinity by which vanilloid receptors recognize capsazepine. Protons were shown to inhibit RTX binding to rat spinal cord membranes. Thus, protons and/or putative proton-generated substances might represent endogenous modulators of vanilloid receptors. A novel vanilloid ligand, phorbol 12-phenylacetate 13-acetate 20-homovanillate (PPAHV), was developed which bound to cultured dorsal root ganglion neurons and induced calcium uptake by them in a non-cooperative fashion. RTX bound to vanilloid receptors in a positive cooperative manner; however, in the presence of PPAHV, cooperative binding was no longer observed. These results suggest that positive cooperativity is a ligand-induced feature rather than an inherent property of vanilloid receptors. Neuroleptic drugs (trifluoperazine and rimcazole) were found to inhibit RTX binding to porcine dorsal horn membranes consistent with a non-competitive or mixed binding mechanism. this interaction may represent a mechanism for their adjuvant analgesic action. In conclusion, spec","PeriodicalId":75414,"journal":{"name":"Acta physiologica Scandinavica. Supplementum","volume":"629 ","pages":"1-68"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19773516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-function relationships in the Ca(2+)-ATPase of sarcoplasmic reticulum studied by use of the substrate analogue CrATP and site-directed mutagenesis. Comparison with the Na+,K(+)-ATPase.","authors":"B Vilsen","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75414,"journal":{"name":"Acta physiologica Scandinavica. Supplementum","volume":"624 ","pages":"1-146"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18493050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of angiotensin receptor subtypes in cerebrovascular regulation in the rat.","authors":"L Näveri","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The present studies were conducted to examine the roles of angiotensin II, angiotensin IV, and the angiotensin receptor subtypes in the cerebral circulation. The effects of angiotensin II, the selective AT1 receptor antagonist losartan, and the selective AT2 receptor ligands, PD 123319 and CGP 42112, on cerebral blood flow autoregulation, were studied during increases and decreases in blood pressure in normotensive rats. Cerebrocortical blood flow was measured by laser-Doppler flowmetry, while systemic blood pressure was either increased by phenylephrine infusion, or decreased by controlled haemorrhage. The effects of angiotensin II, and AT1 and AT2 receptor ligands on the contractility of rat anterior cerebral artery in vitro, were studied using cannulated, perfused vessel segments. The effect of angiotensin IV on cerebral blood flow after experimental subarachnoid haemorrhage, and possible involvement of nitric oxide, was studied in rat. Subarachnoid haemorrhage was simulated by injecting 0.3 ml arterial blood into the cisterna magna, while cerebral blood flow was measured by laser-Doppler flowmetry. The main findings in the present studies were that angiotensin II, the AT1 antagonist losartan, and the AT2 ligands PD 123319 and CGP 42112, shifted the cerebral blood flow autoregulatory range towards higher blood pressures. PD 123319 and CGP 42112 acted as AT2 receptor agonists. In vitro, angiotensin II elicited an AT1 receptor mediated contraction of rat anterior cerebral artery. Angiotensin IV was able to reverse the acute CBF reduction after subarachnoid haemorrhage. No evidence was found to support the involvement of nitric oxide in this response. In conclusion, there is strong evidence supporting a role for the AT2 receptor in the regulation of cerebral circulation. The role of the AT1 receptor is questionable, and the losartan induced autoregulatory shift is possibly mediated indirectly through AT2 receptor stimulation. Although AT1 receptors mediate the angiotensin II induced contraction of rat anterior cerebral artery in vitro, this effect does not explain the effect of losartan on CBF autoregulation. Angiotensin IV increases cerebral blood flow after experimental subarachnoid haemorrhage possibly by dilating cerebral vessels through stimulation of the AT4 receptor.</p>","PeriodicalId":75414,"journal":{"name":"Acta physiologica Scandinavica. Supplementum","volume":"630 ","pages":"1-48"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19589440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}