摘要:

SUMMARY1. In recent years, fine sensory nerve fibres have been detected that are not excited by physiological stimuli, even at potentially tissue damaging intensities. These silent afferents are known to supply knee joint, skin and viscera; in the last case, silent afferents seem to be particularly numerous.2. When an artificial inflammation is induced, many silent afferents develop spike activity, others remain quiescent. Silent afferents that do respond probably have a nociceptive sensory function. Under inflammatory conditions some silent afferents are sensitized to physiological stimuli, others are probably chemospecific.3. Orthodromic activity in silent afferents may sum spatially and temporally in second order neurons with other nociceptive information and may thereby contribute to different pain states. Furthermore, there is evidence that the activation of chemospecific silent afferents may lead to sensitization of nociceptive dorsal horn neurons.4. Some silent afferents probably contain neuropeptides that may be liberated under pathophysiological conditions, such as inflammation.5. Whether certain pathological states can be exclusively attributed to the activation of silent afferents or whether silent afferents sustain the functions of ‘conventional’ nociceptors remains to be clarif

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02579.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. Changes in plasma renin activity (PRA) and in the plasma concentration of aldosterone, adrenocorticotrophic hormone (ACTH) and cortisol in response to an intravenous infusion of the chemoreceptor stimulant almitrine bismesylate (0.2 mg/kg) were studied in two groups of anaesthetized, paralysed and constantly ventilated cats. In one group, the peripheral arterial chemoreceptors remained innervated, whereas in the other they were denervated by bilateral cervical vagotomy and section of the carotid sinus nerves.2. Animals with innervated chemoreceptors (n= 16) reacted to almitrine bismesylate with a significant (P<0.05) increase in both ACTH and cortisol. These responses were not present in cats in which the peripheral arterial chemoreceptors had been surgically denervated (n= 16).3. Plasma renin activity and plasma aldosterone increased with time during experiments on both the chemoreceptor‐intact and chemoreceptor‐denervated cats. Almitrine did not affect the time course of the rise in PRA and plasma aldosterone in either group of animals.4. These data indicate that, under the conditions of our experiments, almitrine induced arterial chemoreceptor reflex mechanisms stimulate ACTH and cortisol release, but has no chemoreceptor‐dependent influence on PRA or plasma aldost

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02580.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. We evaluated the use of non‐radioactive fluorescent‐labelled microspheres (FM) for the measurement of regional myocardial blood flow (RMBF) in an ischaemic sheep model.2. Injection of FM directly into the coronary artery was compared with left atrial injection. There was a good correlation in the measurement of RMBF between these two injection methods (r = 0.92;n= 107 data points). Injection into the coronary artery requires less FM (one twentieth of that required by atrial injection) and is more economical.3. The use of a fluorescent technique without filtering myocardial tissue was investigated. Calibration curves from the fluorescence plus myocardial tissue samples were similar to those of the pure fluorescence samples and both showed a linear relationship between fluorescent intensity and the number of microspheres (r>0.97). These results indicate that the extraction of six fluorescent dyes (blue‐green, yellow‐green, green, orange, red and crimson) directly from the aqueous solution using ethyl acetate is effective.4. A subendocardial ischaemic model was produced by partially occluding the circumflex artery (CxA) with concomitant left atrium (LA) pacing. During ischaemia, the endocardium/epicardium (Endo/Epi) flow ratios in the ischaemic area changed from 1.04 ± 0.12 to 0.47 ± 0.17 (P<0.05; CxA injection) and from 1.08 ± 0.12 to 0.51 ± 0.05 (P<0.05; LA injection). The ratio in the non‐ischaemic area remained unchanged (1.12 ± 0.26 to 1.01 ± 0.22; not significant).5. RMBF calculation using coronary inflow as the reference flow was also compared with that using the traditional method. We found that, in this study in which a non‐filtering technique was applied, using coronary inflow as the reference flow was superior to the conventional dista

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02581.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. Bronchoconstriction can be evoked by electrical stimulation of the vagus nerves in the presence of atropine. We have used novel, highly selective tachykinin receptor antagonists, together with a procedure for on‐line, breath‐by‐breath analysis of total lung resistance (Rl, subtractor method) and dynamic lung compliance (Cdyn), to investigate the role of tachykinins in this response in anaesthetized, paralysed guinea‐pigs.2. In the presence of 1 mg/kg phosphoramidon (a neutral endopeptidase inhibitor), CP 96345 (the non‐peptide NK1selective antagonist) at 200 nmol/kg had no effect on the increase in Rlcaused by vagal stimulation, but significantly inhibited the associated decrease in Cdyn.3. The NK2selective antagonist, MDL 29913 (1 μmol/kg), significantly antagonized the changes in both Rland Cdyn.In the absence of phosphoramidon, MDL 29913 again significantly inhibited the changes in Rland Cdyn, although CP 96345 no longer had any effect.4. The non‐peptide NK2selective antagonist, SR 48968 (100 nmol/kg), also effectively inhibited the responses to vagal stimulation and was more potent than MDL 29913.5. These results emphasize the importance of the NK2receptor system in mediating non‐cholinergic bronchoconstriction evoked by vagal stimulation in

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02582.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. The angiotensin type 1 (AT1) receptor antagonist, losartan (10 mg/kg) was infused intravenously into nine chronically catheterized fetal sheep (125–132 days gestation). Losartan reduced the fetal systolic (P<0.01) and diastolic (P<0.01) pressor response to 5 μg angiotensin II (AngII) i.v. from 27.4 ± 1.5 to 7.4 ± 0.9 and from 17.5 ± 1.3 to 5.4 ± 0.6 mmHg, respectively, after 1h and to 6.1 ± 0.5 and 4.4 ± 0.5 mmHg, respectively, after 2h. Maternal pressor responses to 5 μg AngII i.v. were unchanged. Fetal mean arterial pressure decreased (P<0.05) after losartan administration, but fetal heart rate did not change.2. Fetal haematocrit increased (P<0.05), fetal PO2decreased (P<0.01), PCO2did not change and pH decreased (P<0.01), as did plasma bicarbonate levels (P<0.01) following administration of losartan. Thus, losartan induced a fetal metabolic acidosis.3. Fetal placental blood flow did not change following administration of losartan. In the fetal kidney, losartan caused a decrease in vascular resistance (P<0.01) and an increase in blood flow (P<0.05). Glomerular filtration rate decreased (P<0.05); thus, filtration fraction decreased (P<0.01). There was no change in the fractional reabsorption of sodium and glomerulotubular balance was maintained. Free water clearance decreased (P<0.01) and became negative. Urine flow decreased (P<0.01), the excretion rates of sodium, potassium and chloride did not change, but the urinary sodium:potassium ratio decreased (P<0.05). There was a decrease in lung liquid flow (P<0.05) following losartan.4. It is concluded that the fetal renin‐angiotensin system (RAS) is important in the maintenance of fetal arterial pressure, the regulation of fetal renal blood flow and is essential in the maintenance of fetal glomerular function. Further, these actions of AngII are mediated via functional AT1receptors. These effects of losartan on the fetal cardiovascular system, renal blood flow and function are similar to those observed following captopril administration. Thus, the effects of angiotensin converting enzyme (ACE) inhibition in the foetus are due to the blockade of the fetal RAS and are independent of any direct effects on bradykinin or prostagla

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02583.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. Blood volume was measured weekly using [51Cr]‐labelled red cells in 10 lambs from 3 to 10 weeks of age. Red cell and plasma volumes were calculated using the measured blood volume and haematocrit. Other parameters, including plasma erythropoietin, urea, creatinine and glucose, were measured twice weekly. The results were compared to a group of five lambs that received an infusion of insulin‐like growth factor I (IGF‐I).2. In control lambs, plasma volume increased linearly by 47 ± 7 mL/week over the experimental period. Red cell volume only increased by 10 ± 2 mL/week during weeks 3–7, but then increased by 25 ± 2 mL/week over weeks 7–10. Haematocrit declined from 28.0 ± 1.6 to 24.7 ± 1.7% over weeks 3–7 and then increased to 30.7 ± 1.1% by week 10.3. In 10 control lambs infused for 8 days (starting at 22–26 days of age) with 10 mmol/L HCl, there was a decrease in plasma IGF‐I concentrations, 3 days after the start of infusion. In five lambs infused for 8 days with IGF‐I (6 μg/kg per h) plasma IGF‐I concentration was maintained significantly (P<0.01) higher than that of the controls.4. There was no significant difference in haematocrit, red cell or plasma volumes between the treatment groups and no reticulocytosis was observed. Plasma erythropoietin concentrations did not change over the infusion period in either group.5. Serum urea decreased significantly in the IGF‐I infused group but serum creatinine did not change in either group during the infusion period. In both the groups, there was a significant decrease in glucose, urea and creatinine over weeks 3–10 after birth. There was no difference in growth rates between the two groups.6. Thus, it appears that the observed changes in haematocrit are due to a constant increase in plasma volume with varying rates of red cell volume increases.7. IGF‐I infused at a dose that maintains physiological concentrations and alters protein metabolism does not result in increased erythropoietin or erythropoiesis during

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02584.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. We have shown previously that renal artery stenosis in rats causes enhanced responsiveness to the slow pressor effect of angiotensin II (AngII) and suggested that two‐kidney, one clip (2K1C) hypertension may depend, in part, on changes in responsiveness to the peptide.2. The present experiment was performed in order to investigate whether a degree of renal artery stenosis that was insufficient to raise blood pressure was able to enhance responsiveness to the slow pressor effect of AngII.3. Two to four weeks after placement of a 0.2 mm clip over the left renal artery (2K1C) or a sham operation, some 2K1C rats were normotensive. These rats and the sham rats then received an intravenous infusion of AngII (4 ng/min) for 10 days.4. AngII caused the 2K1C rats to attain significantly higher mean arterial pressure than the sham rats (152 ± 7vs133 ± 7 mmHg) and did not result in water or electrolyte retention in the 2K1C rats.5. These results indicate that normotensive 2K1C rats exhibit enhanced responsiveness to the slow pressor effect of AngII and that the arterial pressure response to renal ischaemia may depend on both AngII formation and responsiveness to the chronic actions of the pept

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02585.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. The effects of extracellular or intracellular pH changes on agonist‐ or depolarization‐induced contractions of the rat tail artery were investigated.2. Vessels were perfused initially (25 min) with physiological salt solution (PSS) at a pressure of 30 mmHg. Perfusion was then continued with calcium‐free PSS containing either 3.0 μmol/L noradrenaline (NA) or 100 mmol/L K+, which had been made either acidotic or alkalotic. Contractile responses to graded concentrations of calcium were assessed.3. A reduction in the intracellular or extracellular pH was induced by the addition of a weak acid (30 mmol/L sodium propionate) or reduction of the concentration of HCO3‐in the PSS, respectively; an elevation of the intracellular or extracellular pH was produced by the addition of a weak base (10 mmol/L trimethylamine) or by increasing HCO3‐, respectively. The PSS was bubbled with 5% CO2/95% O2.4. Lowered intracellular pH did not alter NA‐ or K+‐stimulated contractions. During lowered extracellular pH, contractile responsiveness and peak response were significantly reduced in K+‐stimulated arteries, but were not affected in NA‐stimulated arteries.5. Elevated intracellular pH did not alter NA‐induced contraction, but reduced the sensitivity to K+‐stimulated contractions. Elevated extracellular pH had little effect on the magnitude of K+‐induced contractions, but slightly enhanced (although not significantly) NA‐induced contractions.6. It is concluded that reduced contractile responses to K+during extracellular acidosis are due to the modulation of potential‐operated calcium channels (POC). Alkalotic vasodilatation is mediated by intracellular events and is POC‐modulated, whereas alkalotic vasoconstriction appears to be due to extracellular events and is modulated by receptor

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02586.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. In order to develop a simple, efficient system for the high‐level expression of dopamine receptors in eukaryotic cells, we have studied the effects ofn‐butyrate on the expression of rat D1Adopamine receptor cDNA in mouse fibroblast LTK‐cells as compared with those ofn‐butyrate on endogenous D1receptor levels in opossum kidney cells.2. In the transfected LTK‐cell membranes with pRc/CMV‐D1Areceptor cDNA, a selective D1dopamine antagonist, [3H]‐SCH 23390, exhibited a K4of 0.9 ± 0.1 nmol/L and a Bmaxof 0.35 ± 0.05 pmol/mg protein (n= 5).3. Addition ofn‐butyrate (2–10 mmol/L) to the culture medium for 48 h dose‐dependently increased the D1Areceptor level up to 1.5 ± 0.3 pmol/mg protein (n= 7), although the K4values were not affected. The increase in receptor level was accompanied by an elevation of selective D1agonist‐induced adenylyl cyclase activity.4. In contrast,n‐butyrate treatment (2–10 mmol/L) did not affect either endogenous D1receptor levels or fendoldopam‐induced adenylyl cyclase activity in opossum kidney cells.5. These results suggestn‐butyrate is a useful tool for obtaining high‐level expression of D1Adopamine receptor

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02587.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02588.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY