摘要:

‘We must always guard the liberties of the mind and remember that some degree of heresy is often a sign of health in spiritual life.’ U. S. von Euler,Circulation,26(1962), 1

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09359.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The effects of several 5‐hydroxytryptamine (5‐HT) receptor antagonists were tested in ratsin vivoon the intestinal fluid secretion evoked by cholera toxin. Five receptor antagonists were used, namely 2‐bromolysergic acid diethylamine (2‐bromo‐LSD), granisetron, ketanserin, methysergide and ondansetron. The drugs were used in doses that inhibited the arterial hypertension and/or bradycardia evoked by 5‐HT given i.v. Granisetron and ondansetron markedly diminished cholera‐toxin‐evoked secretion, whereas ketanserin was without any effect. Methysergide also diminished cholera‐toxininduced fluid secretion particularly when the drug was given as an i.v. infusion. The results are considered in relation to the pathophysiology of cholera secretion and to the current views of receptor subtypes for 5‐HT. It is proposed that the receptor involved is a 5‐HT3receptor, possibly also a receptor of the 5‐HT1type. Results from experiments in which 5‐HT (20 mM) was placed in the intestinal lumen to evoke an intestinal secretion suggest that the 5‐HT3receptor is located in the villus tissue. It was also demonstrated that zimeldine, an inhibitor of presynaptic 5‐HT reuptake, diminished choleraic secretion, an effect that may be ascribed to a 5‐HT tachyphylaxis caused by an accumulat

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09360.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The aim of this study was to evaluate the mechanism behind neurogenic fluid secretion in the rat jejunum.In vitro, short‐circuit current (SCC) and potential difference (PD) were measured with the conventional Ussing technique.In vivo, electric parameters and net fluid transport (NFT) were simultaneously recorded with two different techniques. In separatein vivoexperiments alkaline secretion (As) was estimated.In vitro, the chloride channel blocking substance 5‐nitro‐2(‐3‐phenylpropyl‐amino)benzoic acid (NPPB) and the loop diuretic substance furosemide (F) inhibited SCC, whereas the carbonic anhydrase inhibitor acetazolamide (Ace) lacked effect. Noradrenaline inhibited SCC and this effect was antagonized by NPPB and F.In vivo, cholera toxin induced a parallel increase in PD/SCC and fluid secretion. Conversely, mesenteric nerve stimulation (MNS) or administration of the nicotinic antagonist hexamethonium (Hx), concomitantly inhibited PD/SCC and fluid secretion. However, there was a poor correlation between the magnitudes of these effects. F inhibited SCCin vivoand also the SCC‐effect of MNS. However, F had no effect on fluid secretionin vivo, nor on the NFT‐effect of MNS. Jejunal As was stimulated by cholera toxin and MNS significantly inhibited As. The present results challenge the current view on the role of electrogenic chloride secretion in intestinal secretion. Alternative mechanisms are tentat

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09361.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

In isolated human detrusor preparations angiotensin (At)II 10‐9‐10‐5mcaused concentration‐dependent contractions. The contractile effect was immediate, and had an amplitude which at the highest concentration used, 10‐5m, reached 103 ± 16% of the mean contraction produced by K+124 mm(27.6 ± 1.4 mN). The AtII effect was completely blocked by saralasin 10‐6m, but was not affected by pre‐treatment of the preparations with captopril or enalaprilate. There was a marked tachyphylaxis to the actions of the peptide. AtI (10‐8–10‐5m) also caused contractions which were rapidly developing, and subject to a marked tachyphylaxis. At a concentration of 10‐5m, the mean amplitude was 66 ± 9% of the K+‐induced contraction. The contractions were blocked by saralasin 10‐6m, but not by captopril or enalaprilate 10‐5m. In contrast, contractions produced by AtI in rabbit mesenteric arteries were practically abolished by the angiotensin converting enzyme (ACE) inhibitors. The contractions induced by both Ad and AtII were practically abolished after pre‐treatment in a nominally calcium‐free Krebs solution. However, blockade ofl‐type calcium channels by nifedipine 10‐6mreduced the responses to both AtI 10‐6M (by 38 ± 4%) and AtII 10‐6m(by 39 ± 7%), but never abolished the contractions. Bradykinin (Bk; 3 times 10‐8–10‐5m) had a contractile effect in detrusor preparations which varied widely between strips. At a concentration of 3 times 10‐6m, a maximum was reached amounting to 30 ± 10% of the K+‐induced contraction. Bk‐induced contractions were practically abolished (0–3% of K+‐induced contraction) by a 30 min exposure of the preparations to calcium‐free medium. In the presence of nifedipine 10‐6m, the mean response to Bk 10‐5M did not differ significantly from the control value. Thirty min pretreatment with captopril or enalaprilate 10‐5msignificantly increased the Bk 10‐5minduced contractions. These contractions were significantly reduced by pretreatment for 30 min with indomethacin.The results suggest that Ad, AtII, and Bk all have marked contractile effects on isolated human detrusor smooth muscle. The conversion of AtI to AtII seems to occur through an enzyme which cannot be inhibited by

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09362.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

In previous studies on Milan hypertensive (MHS) rats, we found an impaired tubuloglomerular feedback (TGF) response before, during and after development of hypertension. In the present study MHS rats and rats of the Milan normotensive strain (MNS) were investigated after 24 hours of volume depletion (VD) and subsequently after 5% isotonic volume expansion (VE) with respect to whole kidney function, interstitial hydrostatic (Pint) and oncotic (IIint) pressures, stop‐flow pressure characteristics of TGF and changes in early proximal flow rate in response to increased loop of Henle flow. MHS rats had higher mean arterial blood pressure (Pa) than MNS rats (129 vs. 101 mmHg) both after VD and after subsequent VE. No difference in glomerular filtration rate (GFR) was found. Both strains had a low urine flow rate (1.5 μl min‐1) during VD, which increased fourfold after VE. The interstitium was significantly more dehydrated in MHS, as indicated by a more negative net interstitial pressure (Pint–±intt than in MNS (‐1.3 ± 0.3 vs. ± 0.0 ± 0.5 mmHg) after VE. The TGF mechanism was more activated in MHS during volume depletion, as indicated by a larger drop in stop‐flow pressure (Psf) in response to loop of Henle perfusion (7.1 ± 0.7 vs. 4.7 ± 0.2 mmHg,P<0.05). However, during VD the loop of Henle flow that elicited half maximal response in Psf, the turning point (TP), was equally low in MHS and MNS (13.5 ± 0.6 and 14.3 ± 0.4, respectively). After VE, however, TP increased significantly more in MNS to (32.6 ± 2.1 nl min‐1) then in MHS (to 21.8 ± 0.9 nl min‐1,P<0.05). It is concluded that the blunting of the TGF resetting in response to VE in MHS rats may well be of importance in the development of hypert

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09363.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Renal effects of arginine vasopressin and oxytocin were studied in conscious dogs, made water‐diuretic by a waterload equivalent to 2% of body weight. Body water and content of sodium were maintained by separate servo‐controlled infusions. Peptides were infused for 60 min at rates of 50 pg kg‐1min‐1(arginine vasopressin) or 1 ng kg‐1min‐1(oxytocin), either separately or combined. Infusions increased plasma arginine vasopressin to 1.9 ± 0.2 (arginine vasopressin alone) and 1.8 ± 0.3 pg kg‐1(arginine vasopressin plus oxytocin and plasma oxytocin to 72 ± 5 (oxytocin alone) and 77 ± 8 pg ml‐1(oxytocin plus arginine vasopressin). Arginine vasopressin or arginine vasopressin plus oxytocin increased urine osmolality similarly by a factor of 13, decreased urine flow to between 5 and 7% of control and decreased free water clearance. Oxytocin reduced urine flow and free water clearance and increased urine osmolality by a factor of 2. Oxytocin and arginine vasopressin separately increased excretion of sodium from 4 ± 2 to 15 ± 6 μmol min‐1and from 7 ± 4 to 25 ± 13 μmol min‐1, respectively. Arginine vasopressin plus oxytocin led to a pronounced natriuresis (13 ± 4 to 101 ± 27 μmol min‐1). Arginine vasopressin and arginine vasopressin plus oxytocin increased the excretion of potassium by a factor of 2.5. Oxytocin and arginine vasopressin plus oxytocin increased urinary Na+/K+ratio by a factor of 3.7.It is concluded, that oxytocin at plasma concentrations of 70–80 pg ml‐1has modest antidiuretic and natriuretic effects and that the combined action of arginine vasopressin oxytocin may eli

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09364.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Effects of the GTP binding protein (G‐protein) activator NaF on parathyroid hormone (PTH) release, cytoplasmic Ca2+concentration ([Ca2+]1) and cAMP content of bovine as well as normal and pathological human parathyroid cells were studied using precautions to avoid CaF2precipitation. In 0.5 mmexternal Ca2+, NaF inhibited PTH release and lowered the cAMP content by 50–70% of the effects attained with 3.0 mm Ca2+. The NaF‐induced increase of [Ca2+]1was considerably smaller than that obtained with rise of external Ca2+. It seems likely that NaF activates the inhibitory Gi‐protein involved in the regulation of cAMP generation. However, it is unclear whether the sluggish rise of [Ca2+]1induced by NaF is due to a direct effect of a G‐protein on Ca2+entry, or somehow related to the G‐protein mediated formation of inositol 1,4,5‐trisphosphate, which is part of the signal transduction pathway normally initiated by Ca2+binding to its receptor on the parathyroid cell surface. Inhibition of PTH release by NaF probably results from the combined effects on [Ca2+]1and cAMP content. In hyperparathyroidism (HPT) the actions of NaF were not markedly affected despite severe impairments of Ca2+‐inhibited PTH release and Ca2+triggered increase of [Ca2+]1. Consistent with observations of down regulation of the parathyroid Ca2+receptor in HPT, the present results indicate that the disease perturbs signal transduction at a level proximal to the site of

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09365.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Parotid saliva from 12 healthy volunteers was collected prior to and after 5 and 25 min of stimulation at a constant flow rate of 0.25 or 1.0 ml min‐1. In the salivary samples the concentrations of tPA (tissue‐type plasminogen activator), PAI‐1 (plasminogen activator inhibitor type‐1), albumin and total protein were determined and the activity of amylase, tPA and PAI assessed. Presence of both tPA and PAI‐1 antigen was demonstrated in all samples, and in unstimulated saliva the ratio between the activator and its inhibitor was 1:7. Upon stimulation we found a significantly increased concentration of PAI‐1, a less pronounced increase in tPA concentration, unchanged amylase and total protein levels and significantly decreased albumin concentration. tPA activity was significantly reduced after prolonged stimulation which had no effect on PAI activity. In stimulated saliva a significant positive correlation between concentration of tPA and PAI‐1 was demonstrated. Stimulation with citric acid had no effect on output of albumin which is passively filtered from blood, whereas the increase in flow rate corresponded to the significantly increased secretion rate of total protein and amylase which is secreted by gland cells. The secretion pattern of tPA and PAI‐1 differed significantly from that of albumin in showing markedly increased output rate during the stimulation period, and the relative increase in output of PAI‐1 was significantly higher than that of amylase and total protein. Thus, the results from this study suggest an active release of both tPA and its main inhibitor

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09366.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09367.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09368.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY