摘要:

Bradykinin, a stimulator of B1and B2receptors, significantly increased PGI2synthesis and fluid extravasation, as assessed by the increase of organ weight when injected intra‐arterially into the artificially perfused rabbit hindquarters preparation. Diclofenac pretreatment prevented PGI2synthesis and significantly reduced fluid extravasation. Oedema formation and PGI2synthesis were also significantly reduced by a simultaneous infusion of papaverine. Selective stimulation of B1‐type receptors with des‐Arga‐bradykinin was not accompanied by edema formation nor PGI2synthesis but by a significant rise in vascular resistance. The combined application of bradykinin and the selective B1receptor antagonist des‐Arg9‐‐[Leu8]‐bradykinin also resulted in oedema formation and PGI2synthesis, the extent, however, being significantly reduced in comparison to the application of bradykinin only. The data suggest that bradykinin‐induced oedema proceeds from B2receptor stimulation and is potentiated by simultaneous stimulation of B1receptors. The kinin‐induced fluid extravasation seems to be augmented by concomitantly gener

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09141.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

In thiopentone anaesthetized pigs (n= 10), simultaneous recordings of the vasomotor response to local intra‐arterial infusion of endothelin‐1 and ‐3 were performed in three different vascular compartments of the nasal mucosa. Sphenopalatine artery blood flow (reflecting nasal blood flow), nasal cavity volume (representing blood content in capacitance vessels) and laser Doppler flowmeter signal (reflecting superficial mucosal blood flow) increased in response to low doses (4 times 10‐9to 4 × 10‐8moles) of endothelin‐1. In contrast, marked vasoconstriction (up to 50% of arterial blood flow reduction) occurred upon higher doses (4 × 10‐7to 4 × 10‐6moles). Endothelin‐3 (4 × 10‐9to 4 × 10‐6moles) evoked at the highest dose a long‐lasting increase of systemic arterial blood pressure resulting in a 22 × 4% increase in nasal vascular resistance. After local intra‐arterial pretreatment with methylene blue (4 × 10‐4mol), the vasodilatory responses to low doses of endothelin‐1 were abolished for the three vascular parameters studied, whereas the vasoconstrictor responses in resistance and capacitance vessels evoked by higher doses of endothelin‐1 were increased. In contrast, the laser Doppler flowmeter signal reduction in response to endothelin‐1 was markedly attenuated. The vasodilatatory effect of substance P was abolished after methylene blue probably due to interference with effects of endothelium dependent relaxing factor (EDRF). These observations suggest that in the pig nasal mucosain uivo, exogenous endothelin‐1 induces a dose‐dependent reduction of blood flow in resistance and capacitance vessels and in superficial mucosa. The vasodilatation observed in response to low doses of endothelin‐1 seems to be sensitive to methylene blue and similar to the effect for substanc

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09142.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

An indirect immunofluorescence technique was used to study the distribution of neurokinin A immunoreactive (NKA‐IR) nerve fibres in submandibular and parotid glands of the rat. The functional role of neurokinin A on protein and peroxidase secretion in these glands was evaluated by usingin vitromethods. In the parotid gland neurokinin A immunoreactive fibres were mainly distributed around the secretory acini, but some were also in evidence around the stromal blood vessels and ducts. The number of the neurokinin A immunoreactive nerve fibres was lower in the submandibular gland than in the parotid gland. They were mainly distributed around the secretory acini and stromal blood vessels and ducts.In vitro, neurokinin A significantly stimulated the release of total amount of released proteins and peroxidase from parotid gland fragments, while in the submandibular gland only the release of peroxidase was increased. By using SDS polyacrylamide gel electrophoresis (SDS‐PAGE) specific changes were found in the release of proteins after neurokinin A stimulation. The results of the present study demonstrate that neurokinin A immunoreactive nerve fibres are present in the rat parotid and submandibular glands. Their localization around the secretory elements of the glands and the effect of neurokinin Ain vitroexperiments indicates that neurokinin A might have a significant role in the regulation of salivary secret

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09143.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

An altered release of endothelium‐derived vasoactive factors has been implicated in several vasospastic conditions. Since the functional role of the endothelium in the hand vasculature is largely unknown, we examined the effects of ‘endothelial removal’ on vascular reactivity, and the effects of some ‘endothelium‐associated’ substances in isolated human hand veins and arteries. Acetylcholine induced a large relaxation (Emax= 97±1 %) in precontracted hand arteries. The relaxation was abolished by endothelial removal. In hand veins, acetylcholine induced a small relaxation (Emax= 13 ± 4%), which was unaffected by endothelial removal. An endothelium‐dependent relaxation was, however, obtained with high concentrations ( 10‐6mol 1‐1) of the Ca2+ionophore A23187. Contractile responses to noradrenaline, serotonin and prostaglandin F2xdid not differ between vein segments with and without endothelium. Endothelin was a potent constrictor of both veins and arteries. The potency and maximum response did not differ between the two types of vessel. Indomethacin pretreatment of veins did not influence the endothelin‐induced contractions, suggesting that cyclo‐oxygenase products are not involved in the response. In endothelin‐contracted veins and arteries, the prostacyclin analogue iloprost elicited relaxation of similar potency and amplitude. The maximum relaxation in veins was, however, 3 times larger than that produced by prostacyclin itself. Platelet‐activating factor was devoid of contractile and relaxant effects in both veins and arteries. The present study indicates differences between human hand veins and arteries regarding endothelial‐dependent relaxation, and suggests that the modulatory role of endothelium‐derived relaxing factor(s) is small in hand veins. The contractile and relaxant effects of endothelin and iloprost, however, did not di

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09144.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Isolated rat peritoneal mast cells release histamine when superfused with isoosmotic salt or sucrose solutions. The release was ascribed by us to an intracellular ion exchange between potassium and histamine at granule sites, resulting from a flux of cytoplasmic potassium across the granules secondary to the disturbance of the ‘state of equilibrium’ at the cell surface caused by the superfusion (Uvnäset al. 1989). In the present article is shown that the histamine releasing effect is counteracted by the addition of histamine to the superfusion fluid. The inhibition is concentration‐dependent and accompanied by concomitant changes in the potassium efflux. A 50% inhibition of the histamine release requires an external histamine concentration of 40 μm and extrapolation of the equilibrium curve hints at a total inhibition at concentrations around 170 μm.The observations are taken to indicate that reduction of the juxtacellular histamine concentration caused by the superfusion disturbs the histamine equilibrium at the mast cell surface resulting in the activation of the histamine secretory mechanism. In other words, the secretory activity of the mast cell is checked by the juxtacellular concentration of histamine. When the juxtacellular histamine is removed e.g. on isolation procedures, other experimental situations such as superfusion, or by consumptionin vivothe mast cell delivers histamine to restore the juxtacellular equ

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09145.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The calmodulin inhibitor compound 48/80 has previously been shown to arrest axonal transportin vitroin the regenerating frog sciatic nerve. The inhibition was limited to the outgrowth region of nerves, which had been allowed to regeneratein vivofor 6 days after a crush lesion, before they were incubated with or without drugsin vitroovernight. The effects of compound 48/80 on the regenerating nerve were further investigated. A concentration of compound 48/80 (50 μgml‐1), which effectively inhibits axonal transport, did not cause observable changes of the microtubules of regenerating axons in the outgrowth region as judged by electron microscopy. Furthermore, it was shown that also a lower concentration (25 μgml‐1) inhibited axonal transport. As a measure of possible metabolic effects, the level of ATP was assessed in the regenerating nerve after exposure to compound 48/80. Compound 48/80 at 25 μgml‐1did not change the level of ATP in the nerve. The assembly of bovine brain microtubule proteins in a cell‐free system was unaffected by 25 μgml‐1of compound 48/80 and slightly inhibited by 50 μgml‐1. At higher concentrations (>100 μgml‐1) assembly of microtubules appeared stimulated, and microtubule spirals as well as closely aligned microtubules could be seen. These effects appeared to be unrelated to the transport effects. The present results indicate that compound 48/80 arrests axonal transport via mechanisms other than destruction of axonal microtubules or interference with the energy metabolism. It is possible that these mechanisms involve inhibition of calmodulin‐regulated events essen

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09146.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Ruthenium red (3 × 10‐4M)aerosol attenuated the cough induced by nebulized citric acid in conscious guinea‐pigs. Citric acid‐induced coughing is mediated via capsaicin‐sensitive neurons. However, cigarette smoke‐induced coughing, which involves capsaicin‐resistant mechanisms, was not affected by ruthenium red. In conclusion, ruthenium red selectively inhibits the capsaicin, resiniferatoxin and citric acid‐induced excitation of the sensory nerves as revealed by calcitonin gene‐related peptide‐like immunoreactivity release, bronchoconstriction and coughing, suggesting that these agents share a common m

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09147.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Microelectrode multi‐unit recordings of muscle nerve sympathetic activity, primarily involved in blood pressure regulation, were made from the right peroneal nerve in 10 healthy subjects during exposure to cold inside a box used for hypothermic surgery. Blood pressure was monitored by an automatic cuff applied to the left arm. Heart activity (ECG) and the temperature inside the box were monitored.Muscle nerve sympathetic activity outflow and blood pressure were stable during 15 minutes initial rest at 22.7 ± 0.3 °C (mean ± SEM). All subjects increased muscle nerve sympathetic activity and blood pressure with lowering of ambient temperature. The box temperature was 10.5 ± 0.3 °C at the end of the cooling period. With rewarming the changes in muscle nerve sympathetic activity and blood pressure were reversed. Mean outflows of muscle nerve sympathetic activity during initial rest, final phase of cooling period, and post‐rewarming were 20.3 ± 2.7, 26.6 ± 3.2 and 20.2 ± 2.8 burst min‐1respectively. Systolic blood pressure during the same periods was 118 ± 3, 131±4 and 120±4 mmHg, respectively, whereas corresponding values for diastolic blood pressure were 73±2, 82 ± 2 and 75 ± 2 mmHg (P<0.001 for all variables; (ANOVA).It is concluded that muscle nerve sympathetic activity, while not regarded as being involved in body temperature regulation, is under the influence of ambient temperature and contributes to blood pressure elevation in a cold environment. The increase in muscle nerve sympathetic activity may play a role in body temperature regulation by preserving heat within the central core or by inducing heat production by small muscles in the vessel walls, the latter possibility being in agreement with recent observations suggesting that smooth muscles in limb vasculature may contribu

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09148.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Isolated papillary muscles from guinea‐pig right ventricles were used (temperature 33 °C, stimulation frequency 0.5 Hz). Isometric twitch and action potentials were recorded. Upon addition of 2, 3‐butanedionemonoxime (BDM) (2 mm) the peak twitch force was reduced from 4.17 ± 0.4 mN/mm2to 1.68 ± 0.3 mN/mm2(n =9,P<0.001). The time course of the isometric twitch was slightly altered. Time to peak tension (TPT) was reduced by 12.0 ± 3% (n =9,P<0.001) whereas time to half relaxation (THR) was left unaffected. The rate of rise offorce was reduced by 35 ± 3.2 mN/mm2s i.e. 46 ± 3 %. The action potential duration and amplitude was not significantly changed by the drug. The shape of the curve relating peak twitch force of an extra beat to the preceding test interval, i.e. mechanical restitution, was affected by 2 mM 2,3‐butanedionemonoxime. The curve reached its maximum faster after addition of the drug. Maximum postextrasystolic potentiation (force in response to the prepreceding test interval) was 3.2 ± 0.4 mN/mm2in 2 mm 2,3‐butanedionemonoxime and 7.6 ± 0.7 mN/mm2in control (n= 6). However the percentage potentiation was very similar in control (82%) and in presence of 2,3‐butanedionemonoxime (91%). Peak twitch force in relation to peak force of the preceding potentiated contraction during decay of postextrasystolic potentiation was analysed. There was a linear relation between the variables, the slope being 0.34 ± 0.04 in control and 0.30 ± 0.02 in 2J‐butane dionemonoxime. This suggests that the drug is without an action on the fraction of calcium recirculating within the cell. As previously suggested the negative inotropic action of BDM can be explained by an action on cross‐bridge kinetics, however the effects on the mechanical restitution curve suggests an additional action on the calcium handling by the

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09149.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The mechanisms influencing arterial blood pressure and heart rate were studied in conscious foxhounds after chronic sino‐aortic and cardiopulmonary denervation (N= 6). In previous investigations it was shown, that this denervation produces hypertension and tachycardia, which is confirmed by the present study: Mean arterial blood pressure increased from 101 ± 3 to 123 ± 6 mmHg (P<0.05), and heart rate rose from 85 ± 6 to 124 ± 5 beats min‐l(P<0.001). The variability of mean arterial blood pressure, but not that of heart rate increased (from 6 ± 1 to 22 ± 2 mmHg (P<0.001)). The administration of the a‐adrenergic blocker prazosin reduced both mean arterial blood pressure (‐33 ± 8 mmHg,P<0.01) and its variability (‐ 12 ± 1 mmHg,P<0.01), thus suggesting an α‐adrenergic mediated hypertension. β‐blockade by propranolol blunted the heart rate increase (‐ 24 ± 5 beats min‐1P<0.05). Although plasma renin activity increased in the denervated dogs, converting enzyme inhibition had little effect on mean arterial blood pressure and heart rate. In conclusion, chronic sino‐aortic and cardiopulmonary denervation enhances the α and β‐adrenergic component of car diovascular control in a different fashion. While the α‐adrenergic component induces fluctuations around an elevated arterial blood pressure level, the β‐adrenergic tone to the heart increases without

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09150.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY