摘要:

SUMMARY1. Recent findings have further helped to elucidate the mechanisms involved in the transmission and modulation of pain. It is now known that pain, inflammation and nervous system damage result in a number of changes in peripheral nerves, spinal cord and supraspinal structures. These changes themselves may be responsible for the development and maintenance of chronic pain syndromes.2. In response to these findings, new agents and techniques have been applied in the clinical setting and new approaches have been developed to use existing agents more effectively. This review presents some of the findings from recent studies and the implications they have for the management of pain.

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01921.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. In recent years, there has been considerable interest in the possibility that insulin may have important cardiovascular as well as metabolic actions. Perhaps the best documented cardiovascular effect of insulin is to cause peripheral vasodilation, especially in skeletal muscle. Hyperinsulinaemia also stimulates sympathetic activity and causes antinatriuresis, but these effects may be linked, at least in part, to the metabolic actions of insulin that elicit peripheral vasodilation and a tendency toward hypotension. Normal, fasting levels of insulin appear to have very little influence on peripheral vascular resistance, sympathetic activity or renal sodium excretion.2. Decreased sensitivity of the peripheral tissues to the metabolic effects of insulin and compensatory hyperinsulinaemia have been postulated to play key roles in the pathophysiology of diseases such as hypertension and atherosclerosis. Although impaired insulin action (insulin resistance) and hyperinsulinaemia often accompany essential hypertension, especially when associated with obesity, there is currently little direct evidence for a cause and effect relationship between insulin resistance, hyperinsulinaemia and increased arterial pressure. Chronic increases in plasma insulin levels in dogs and humans have not been shown to cause hypertension, although hyperinsulinaemia raises blood pressure in rats.3. Further research is needed to determine whether there are pathophysiological conditions or genetic factors that may predispose humans to a hypertensive effect of hyperinsulinaemia and/or insulin resistance.

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01922.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. Baroreflex control of heart rate (HR) has been studied in normotensive (NT) and hypertensive (HT) awake and anaesthetized animals and man, but baroreflex control of sympathetic nerve activity has not been well studied. We investigated baroreflex control of HR and renal sympathetic nerve activity (RSNA) over a wide range of arterial pressure (AP) in conscious and isoflurane (ISO) anaesthetized NT and HT rabbits.2. Animals were instrumented to record AP, HR and RSNA. Hypertension was accomplished by renal encapsulation. AP‐HR and AP‐RSNA baroreflex function curves were obtained while awake and after 1.0, 1.5, 2.0 and 2.5% ISO. All baroreflex curves were fit to sigmoid or exponential functions.3. In conscious rabbits, HT for 3–5 weeks, AP was significantly higher (75.6 ± 0.8vs102.3 ± 8.9 mmHg); HR significantly lower (218.0 ± 5.5vs189.5 ± 5.5 beats/min); and RSNA not different than NT rabbits (14.9 ± 2.2 vs 9.9 ± 3.2% max RSNA).4. ISO shifted AP‐HR and AP‐RSNA baroreflex curves to the left in NT and HT animals, and significantly attenuated baroreflex range and slope. At low ISO concentrations, baroreflex compensation for decreases in AP is limited to small increases in HR and sympathetic nerve activity. At higher ISO concentrations, baroreflex responses to decreases in AP are lost. RSNA responses to increases in AP are preserved with increasing ISO concentrations while HR responses are progressively attenuated. The sole effect of chronic hypertension was to shift the AP‐HR and AP‐RSNA barocurves to the right along the pressure axis in both conscious and ISO anaesthetized animals with no additional change in range or slope.5. At this stage of hypertension development, ISO anaesthesia affects baroreflex function equally in normotensive and h

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01923.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. The aim was to compare the effect of N‐type calcium channel blockade by ω‐conotoxin GVIA (ω‐CTX) with α1‐adrenoceptor or L‐type calcium channel blockade on postural adaptation in conscious rabbits.2. Orthostatic responses were assessed by rapidly tilting the rabbits through 90° for 1 min. Tilts were performed before, 30 and 60 min after i.v. bolus administration of vehicle (propylene glycol 0.17mL/kg; n = 8), prazosin (0.5mg/kg;n= 8), felodipine (30μg/kg;n= 8) or ω‐CTX (3&7 μg/kg;n =9).3. Prazosin, felodipine or ω‐CTX caused significant falls in mean arterial pressure (MAP) with corresponding increases in heart rate (HR). Vehicle administration had no effect on MAP but caused a small fall in HR.4. Before drug or vehicle administration, a small rise in MAP and HR occurred in response to tilt in all rabbits. In the vehicle treatment group, similar responses were observed to tilt at 30 and 60 min. Postural hypotension was observed in the prazosin treatment group, but not following administration of felodipine. Tilts 30 and 60 min after ω‐CTX (3μg/kg) caused an increase in HR but no change in MAP, different to the small pressor response observed following vehicle administration. However, following administration of ω‐CTX 7 μg/kg (total dose, 10μg/kg), significant falls in MAP with tachycardia were observed in response to tilt.5. In conclusion, orthostatic hypotension was observed following acute αl‐adrenoceptor or N‐type calcium channel blockade in the conscious rabbit. These findings are compatible with the expectation that agents which are directly sympatholytic interfere with postural adaptation. In contrast, L‐type calcium channel antagonism with felodipin

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01924.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. Simultaneous recordings of tension and [Ca2+]iduring NANC‐mediated relaxation were made in the rat anococcygeus muscle under various conditions.2. In muscles precontracted with guanethidine, nitrergic stimulations at 2 Hz produced a rapid decrease in both the tension and [Ca2+]i.3. The nitric oxide synthase inhibitor,NG‐nitro‐L‐Arginine (NOLA, 100 μmol/L) completely abolished the decreases in the [Ca2+]iand force response of the NANC‐mediated relaxation.4. Noradrenergic‐mediated contractions elicited by electrical field stimulation were potentiated by the addition of NOLA. In the absence of NOLA, the motor responses were larger in magnitude at 10 Hz stimulation than at 2 Hz. After NOLA, both the force response and the associated rise in [Ca2+]iwere substantially increased in comparison to the control stimulations. Proportionately the potentiation of the 2 Hz response was of a far greater magnitude than that of the 10 Hz response.5. The guanylate cyclase inhibitor methylene blue (10 μmol/ L), partially inhibited the force and [Ca2+]iresponse of the NANC relaxation.6. Following exposure of the muscles to the sarcoplasmic reticulum Ca2+‐ATPase inhibitor, cyclopiazonic acid, (10 μmol/ L) the responses to NANC stimulation were inhibited. The attenuated relaxation response displayed a bi‐phasic timecourse and the Ca2+change in comparison to that of the control was markedly smaller. In some cases, a relaxation was observed with no detectable change in the [Ca2+]i.7. The results suggest that part of the relaxation response observed with NANC‐mediated relaxation in the rat anococcygeus is dependent on Ca2+sequestration into the sarcoplasmic reticulum. However, other Ca2+lowering mechanisms and possible Ca2+independent mechanisms may also contribute to the NANC

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01925.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. Simultaneous measurements of intracellular membrane potential and myogenic tone of proximal segments of the rat middle cerebral artery, mounted in a small vessel myograph, were made at two levels of passive wall tension.2. At low levels of passive tension (less than 0.25mN/mm) vessels had a resting membrane potential of approximately ‐65mV. Addition of KCl (5–60 mmol/L), BaCl2(0.01–3 mmol/L) or tetraethylammonium (TEA; 0.1–3 mmol/L) resulted in a concentration‐dependent depolarization, to approximately—40 mV, generally associated with a contractile response. After the application of high levels of passive tension (to approximately 2mN/mm maximum) the resting membrane potential of the smooth muscle cells was—40 to—45 mV. This more positive membrane potential was generally associated with an increase in myogenic tone of the vessel. Under these conditions, addition of 5–20 mmol/L KCl resulted in a strong hyperpolarization of the cell along with a concomitant decrease in myogenic tone of the artery. The hyperpolarization and vasorelaxation induced by KCl (5–20 mmol/L) were blocked by BaCl2(0.5–1 mmol/L).3. While the addition of ryanodine (10 μmol/L) to vessels under low tension had no effect, when added to a vessel under high tension, this agent caused a rhythmic oscillation in membrane potential. This oscillation was augmented by BaCl2(1mmol/L) and inhibited by nifedipine (10nmol/L) and 4‐aminopyridine (1 mmol/L).4. This study suggests that the electrophysiological and mechanical properties of the isolated rat middle cerebral artery depend on the passive resting conditions under which the vessel is studied. The depolarization of membrane potential observed with increased passive tension appears to result from the closure of an inward rectifying K+channel. These results indicate that the inward rectifying K+channel plays an important role in regulating vascular reactivity due to its functional dependence on the mechanical st

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01926.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. Experiments were designed to evaluate the hypothesis that cyclo‐oxygenase products modulate the influence of angiotensin II (AII) on the renal juxtamedullary microvasculature of enalaprilat‐treated rats.2. Thein vitroblood‐perfused juxtamedullary nephron technique was utilized to provide access to afferent arterioles, efferent arterioles and descending vasa recta located in the outer stripe of the outer medulla.3. Baseline afferent arteriolar diameter was 20.8 ± 1.9 μm in kidneys subjected to cyclo‐oxygenase blockade (1μmol/L piroxicam), a value significantly lower than that observed in untreated kidneys (26.1 ± 1.0 μm). Baseline diameters of efferent arterioles and outer medullary descending vasa recta did not differ between untreated and piroxicam‐treated groups.4. Topical application of 1 nmol/L AII reduced blood flow through outer medullary descending vasa recta by 22 ± 6% in untreated kidneys and by 24 ± 7% in piroxicam‐treated kidneys.5. In untreated kidneys, AII (0.01–100nmol/L) produced concentration‐dependent afferent and efferent arteriolar constrictor responses of similar magnitudes. Neither afferent nor efferent arteriolar AII responsiveness was significantly altered in piroxicam‐treated kidneys, although afferent responses exceeded efferent responses at AII concentrations ≥ 10 nmol/L.6. We conclude that endogenous cyclo‐oxygenase products exert a vasodilator influence on juxtamedullary afferent arterioles under baseline conditions. Although cyclo‐oxygenase inhibition had little effect on juxtamedullary microvascular responses to AII, the response to high AII concentrations may be modulated by cyclo‐oxygenase products in a manner which delicately alters the relative influence of the peptide on

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01927.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. This study was designed to elucidate the effects of guar gum, a dietary fibre, on changes in prostanoid contents induced by 1,2‐dimethylhydrazine, a carcinogenic agent, in rat colonic mucosa.2. Prostanoid contents were determined using high performance liquid chromatography; five prostanoids, namely 6‐keto‐prostaglandin F1α, prostaglandin F2α, prostaglandin E2, prostaglandin D2and thromboxane B2, were detected.3. Four subcutaneous injections of dimethylhydrazine, 60 mg/kg every 6 days, increased the mucosal concentrations of prostaglandin E2and thromboxane B2by approximately 50%. Other prostanoids did not change significantly throughout the experiments.4. In rats treated with dimethylhydrazine and a fibre diet a significant increase in thromboxane B2content was not observed, although a significant increase in prostaglandin E2content was observed. These effects were observed in rats fed with fibre diet over 20 days but not observed in rats fed with fibre diet over 10 days.5. From these results and the report that aspirin use at low doses is effective in the reduction of the risk of fatal colonic cancer, inhibiting thromboxane B2synthesis by fibre diet might he involved in the protective effect against the occurrence of colonic

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01928.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. The aim of the present study was to evaluate whether postural blood pressure (BP) change could predict office‐daytime BP disparity and the nocturnal BP fall in young, mild essential hypertensives. We investigated 411 males aged between 18 and 45 years with never treated borderline to mild hypertension. BP was measured three times after a 5 min rest in the supine position and thereafter three times after 2 min of standing. The mean of six BP measurements obtained during two visits in the lying position was defined as office BP.2. Twenty‐four hour ambulatory BP monitoring was performed with either the A and D TM‐2420 model 7 or the ICR Spacelabs 90207. BP values were averaged for day—and nighttime periods. The nocturnal BP fall was defined as the difference between the average day—and night‐time BP.3. The standing‐lying difference was significantly inversely correlated with the office‐daytime difference for both systolic blood pressure (SBP) (r = ‐0.34,P0.001) and diastolic blood pressure (DBP) (r = ‐0.24,P0.001). These correlations did not change when the obese subjects (body mass index>30 kg/m2) were excluded from the analysis. No significant correlation between standing‐lying difference and nocturnal BP fall was found.4. Our results indicate that white coat hypertension assessed as the office‐daytime BP disparity is partially related (in a negative fashion) to the BP reaction to standing. The postural BP change does not predict nocturnal BP fall in young, mild

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01929.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. We compared endothelial regeneration and intimal thickening after endothelial denudation between normal and sclerotic carotid arteries (CA). Endothelial denudation of the right CA of rabbits formed intimal thickening covered with regenerated endothelial cells (EC) in 6 weeks, which was considered as the sclerosis model. Both CA were then denuded. Morphological and immunohistochemical studies using antibodies for proliferating cell nuclear antigen (PCNA), von Willebrand factor and macrophages were performed.2. Regeneration of EC were observed 24h after denudation on both CA, but completed earlier in the double‐denuded right CA. The density of EC in both CA increased after regeneration and gradually decreased afterwards.3. After a single denudation on the left CA, PCNA‐positive cells clearly appeared in 24h, markedly increased in 72h both in the intima and media, then greatly decreased in 4 and 6 weeks.4. After a double denudation of the right CA, enhancement of the intimal hyperplasia was observed. PCNA‐positive cells markedly increased in 1 week and remained significantly increased in 6 weeks both in the intima and the media.5. We concluded from these results that the repeated endothelial denudation caused more sustained proliferation of smooth muscle cells which led to an enhancement of the intimal hyperp

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01930.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY