摘要:

SUMMARY1. This is a review of the literature on the subject of the effects of cholinesters and their agonists on sensory nerve endings.2. The present‐day view is that acetylcholine (ACh) has an excitatory action on some cutaneous receptors. Responses appear to be limited to receptors served by small myelinated and un‐myelinated axons where responsiveness is multimodal; that is, the receptors are activated by noxious thermal and mechanical stimulation.3. The possible role played by acetylcholine in sensory transduction processes is discussed, as are other explanations for the presence of nicotinic cholinergic receptors on the terminals of cutaneous receptors.4. The excitatory action of ACh and succinylcholine (SCh) on muscle spindles is described. Two possible mechanisms are considered: a direct depolarizing action on the nerve terminals and indirect excitation, brought about by a contracture of the intrafusal fibres on which the sensory endings lie.5. The technique of using SCh in combination with fusimotor stimulation is described. This has provided new information about the internal workings of muscle spindles. Brief mention is also made of the action of SCh on tendon organs and joint receptors.6. It is concluded that a direct action by cholinesters is restricted to receptors served by small axons with multimodal functions. The precise role of such an action remains the subject of speculation. Possible clinical significance is discus

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02741.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. Over the past decade major advances in molecular cell biology have greatly increased our understanding of the way in which many growth factor genes are expressed and regulated. This knowledge is currently being translated into investigations of the cardiovascular system.2. Two growth factor families appear to play particularly important roles, the fibroblast growth factors and the transforming growth factors‐β. These are multifunctional growth factors capable of remodelling the vasculature through their effects on cell migration, proliferation and matrix formation.3. An understanding of their regulation, properties and nature of their receptors is providing novel insights into the physiology and pathobiology of the vasculature. It is also providing highly specific targets for future thera

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02742.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. The role of genetically determined changes in adrenal steroid production, metabolism and action in the pathogenesis of cardiovascular disease in man is considered by studying three loci that are important in corticosteroid function.2. Variation at the glucocorticoid receptor locus can be identified as a biallelic restriction fragment length polymorphism (Bcl1); subjects with contrasting genotypes show altered skin vasoconstrictor responses to topically applied budesonide without any significant change in leucocyte receptor binding characteristics.3. In a case control study of patients with essential hypertension, we have shown evidence of reduced 11β‐hydroxysteroid dehydrogenase activity, with an elevated ratio of cortisol to cortisone metabolites in urine.4. The genes encoding 11β‐hydroxylase and aldosterone synthase are highly homologous. Studies in the Milan hypertensive rat show variation at this locus, which may account for the increased steroid synthesis noted in the hypertensive strain; in man, a chimaeric gene comprising 5’ regulatory regions from 11β‐hydroxylase and 3’ coding sequence from aldosterone synthase accounts for the autosomal dominant condition Dexamethasone Suppressible Hyperaldosteronism. Variation in the precise location of the crossover site between the two genes does not account for the observed phenotypic heterogeneity in this condition.5. Measurement of basal plasma steroid levels in subjects with essential hypertension show an increased ratio of 11‐deoxycortisol/cortisol, consistent with reduced activity of 11β‐hydroxylase in the zona fasciculata.6. In summary, three loci involved in corticosteroid synthesis, metabolism and action can independently affect cardiovascular phenotypes; their roles in determining pathophysiological changes, including hypertension, rem

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02743.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. A patient with severe hypertension was found to have mildly impaired 11β‐hydroxysteroid dehydrogenase (11β‐HSD) activity on the basis of urinary steroid metabolite ratios, low plasma aldosterone, angiotensin II and renin levels and marginally low levels of plasma potassium.2. The patient also had a compulsively high salt intake.3. We tested the hypothesis that high salt intake may affect 11β‐HSD activity.4. High salt intake in normal subjects did not significantly alter either blood pressure or 11β‐HSD activity.5. We suggest that the potentially small hypertensive effect of the partial enzyme deficiency in our patient, also reported in patients with essential hypertension, has been markedly amplified by the very high

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02744.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. This study has pharmacologically characterized endothelin (ET) receptor subtype(s) mediating contraction and enhancement of adrenergic contraction in guinea‐pig pulmonary artery. Isometric tension of the isolated endothelium‐denuded ring preparations was measured in the presence of indomethacin (10−5mol/L) andNG‐nitro‐L‐arginine methyl ester (l‐NAME; 3X10−4mol/L) to exclude a mechanism via endothelium, cyclo‐oxygenase‐generated eicosanoids and nitric oxide.2. In the additional presence of tetrodotoxin (TTX; 3X10−7mol/L), ET‐1 (10−11‐10−7mol/L) concentration‐dependently contracted the preparations. The rank order of potency to contract the preparations among ET receptor agonists was ET‐1, sarafotoxin (STX) 6b>ET‐3>IRL 1620, STX 6c. BQ‐123 (7X10−7‐7X10−6mol/L) concentration‐dependently shifted the concentration‐contraction curve for ET‐1 to the right in a parallel manner. Pretreatment with STX 6c (3X10−7mol/L for 30 min) did not significantly desensitize contractions to ET‐1, ET‐3 or IRL 1620 (P>0.05;t‐test, 10 d. f.).3. ET‐1 (10−10‐10−9mol/L) and STX 6b (10−9‐10−8mol/L) significantly enhanced the electrical field stimulation‐induced contraction in a BQ‐123‐sensitive manner (P<0.05;t‐test, 24–38 d.f.), while ET‐3 (10−11‐10−8mol/L) and STX 6c (10−11‐10−7mol/L) did not affect contractions. ET‐1 (10−11mol/L) significantly enhanced contractions to exogenous nor‐adrenaline in the presence of TTX (3X10−7mol/L) (P<0.05;t‐test, 16 d.f.).4. These data indicate that the BQ‐123‐sensitive ETArec

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02745.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. Left ventricular interstitial adenosine and cardiac function were studied in open chest rats during adrenaline stimulation and P1‐purinoceptor antagonism with 8‐cyclopentyl‐1,3‐dimethylxanthine (8‐CPT).2. Cardiac microdialysate adenosine concentration was 0.10±0.01 μmol/L (n= 24) under basal conditions, giving an estimated interstitial adenosine concentration of 0.27 μmol/L. Stimulation with 3.2 and 8.0 μg/kg per min adrenaline increased the rate‐pressure product (heart rate X systolic blood pressure) by 72 and 157%, respectively, and increased dialysate adenosine to 0.26±0.04 and 0.65±0.11 μmol/L (n= 12), respectively (interstitial concentrations of approximately 0.70 and 1.76 μmol/L).3. Treatment with 60 μg/kg per min 8‐CPT did not alter basal adenosine concentrations, but potentiated elevations in dialysate adenosine during infusion of 3.2 and 8.0 μg/kg per min adrenaline to 0.54±0.10 and 1.30±0.22 μmol/L, respectively (n= 12). Basal function and the response to 8.0 μg/kg per min adrenaline were unaltered by 8‐CPT, whereas elevations in heart rate and rate‐pressure product during stimulation with 3.2 μg/kg per min adrenaline were enhanced by 8‐CPT (by up to 30%).4. Studies in isolated hearts confirmed the inhibitory potency of 8‐CPT at A1vsA2P1‐purinoceptors (e.g. pKBof 7.7±0.2 and 6.4±0.1 for 5′‐N‐ethyl carboxamidoadenosine‐mediated bradycardia and vasodilatation, respectively;n= 6). Studies in intact animals verified effective A1blockade by 60 μg/kg per min 8‐CPT, but also revealed some inhibition of A2‐mediated responses.5. In conclusion, the data show that cardiac interstitial adenosine levels exist within a physiologically active rangein vivoand increase dose‐dependently during graded adrenaline stimulation. Adenosine receptor antagonism enhances elevations in interstitial adenosine and modifies functional responses to moderate, but not high, doses of adrenaline. Whether 8‐CPT‐dependent elevations in interstitial adenosine are due to A1inhibitionvsinhibition o

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02746.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. The release of endogenous noradrenaline (NA) and adenyl purine (ATP, ADP, AMP and adenosine) from the rabbit ear artery, evoked by electrical stimulation (ES; 16Hz), was examined.2. ES evoked a significant release of NA and adenyl purine; the ratio of the amount of total purine released to NA released was approximately 180 on a molar base.3. ES‐evoked purine release was significantly reduced by the denudation of the endothelium and abolished by the α1‐adrenoceptor antagonist, prazosin (1 μmol/L).4. ES‐evoked NA release was significantly reduced by a P1‐purinoceptor antagonist, 8‐sulfophenyl theophylline (8SPT). Purine release was slightly reduced by 8SPT.5. These results suggest that endogenous NA released by ES results in the release of a large amount of purine, which may, in turn, increase the release of NA by acting on prejunctional purinoceptors on sympathetic nerv

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02747.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. The relationship of cigarette smoking to blood pressure and serum lipids and lipoproteins was studied in 7608 men, ranging from 40 to 59 years of age. Analyses were performed separately for non‐drinkers and drinkers.2. After adjusting age and body mass index (BMI) in non‐drinkers and age, BMI and alcohol intake in drinkers in forward stepwise multiple regression analysis, there was a dose‐dependent negative relationship between cigarette smoking and diastolic blood pressure (DBP) and high density lipoprotein cholesterol (HDL‐C), regardless of drinking habit. There was a dose‐dependent positive relationship between cigarette smoking and the ratio of total cholesterol (TC) to HDL‐C (TC:HDL‐C) in non‐drinkers, but not in drinkers. There was a dose‐dependent negative relationship between cigarette smoking and TC and a positive relationship between cigarette smoking and triglycerides (TG) in drinkers, but not in non‐drinkers.3. After matching age and BMI in non‐drinkers, subjects who smoked more than 30 cigarettes/day had significantly lower mean values of systolic blood pressure (SBP; 4.3%;P<0.05), DBP (3.0%;P<0.01) and HDL‐C (15.5%;P<0.01) and higher mean values of TC:HDL‐C (25.0%;P<0.01), TG (46.8%;P<0.01) and β‐lipoprotein (12.0%;P<0.01) than non‐smokers. In drinkers, after matching age, BMI, and alcohol intake, subjects who smoked more than 30 cigarettes/day had significantly lower mean values of SBP (2.8%;P<0.05), DBP (4.8%;P<0.01), HDL‐C (17.3%;P<0.01) and TC (4.4%;P<0.01) and higher mean values of TC:HDL‐C (15.4%;P<0.01) and TG (45.1%;P<0.01) than non‐smokers.4. Although the results are somewhat variable, the present study reveals that cigarette smoking is negatively associated with SBP and DBP and unfavourably associated with lipids and lipopr

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02748.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. The role of nitric oxide (NO) in congestive heart failure was investigated by studying the acute haemodynamic, hormonal and renal effects ofNG‐monomethyl‐l‐arginine (l‐NMMA), a nitric oxide inhibitor, given as incremental bolus doses in six sheep before (normal) and after induction of heart failure (HF) by rapid left ventricular pacing (LVP).2.l‐NMMA caused significant initial dose‐dependent rises in left ventricular systolic pressure, mean arterial pressure (MAP), peripheral resistance (PR) and left atrial pressure and declines in cardiac output in both normal and HF states (maximum response in 2–6 min). These responses were all but abolished whenl‐arginine was given concurrently withl‐NMMA. The dose‐response curve for thel‐NMMA‐induced rise in MAP was shifted to the right following LVP (P<0.05), which is consistent with previous observations of blunted NO synthase activity in HF. A subsequent decline in MAP and PR to below prebolus levels was observed 30–60 min afterl‐NMMA administration in the paced state. No significant hormonal or renal effects were observed.3. In conclusion, the present study confirms the important haemodynamic role played by endogenous NO in the normal state and demonstrates a blunted pressor response to NO inhibition in

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02749.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. Endogenous polyamines play a key role in mediating cellular growth and differentiation. Hypertension is associated with structural modifications of the circulatory system, a process that may be facilitated by polyamines. In this study, we examined whether there are elevated polyamine concentrations in the cardiovascular tissues of spontaneously hypertensive rats (SHR) relative to Wistar‐Kyoto (WKY) rats. We also determined the chronic effect of 2% difluoromethylornithine (DFMO; a polyamine biosynthesis inhibitor) on tissue polyamines and hypertension.2. SHR and WKY rats were treated with either 2% DFMO or drug‐free drinking water; blood pressure was measured on alternate days and tissue polyamines were analysed at the end of the study.3. We found that spermidine and spermine concentrations were markedly raised in the ventricles, resistance vessels and liver of the SHR, in comparison with corresponding tissues of WKY rats. DFMO did not affect SHR resistance vessel and liver polyamines, although spermidine in the ventricles was reduced. The blood pressure of neither SHR nor WKY rats was affected by DFMO.4. In conclusion, this study shows for the first time a raised concentration of polyamines in the resistance vasculature of the SHR, in relation to their normotensive counterparts. The inability of DFMO to significantly reduce tissue polyamines in this study is in contrast to the effectiveness of 2% DFMO in other hypertension models, suggesting that polyamine homeostasis in this model may be stringently regula

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02750.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY