摘要:

SUMMARY1. The preventive effects of monatepil, a new calcium antagonist with α1‐adrenoceptor blocking activity, on ischaemic electrocardiographic changes in rat models of vasospastic angina were evaluated and compared with those of the existing calcium antagonists (diltiazem, verapamil, nicardipine and nifedipine).2. In order to assess the contribution of the α1‐adrenoceptor blocking action of monatepil to its anti‐vasospastic action, the anti‐ST depression effect of prazosin, an α1‐adrenoceptor blocker, was also examined.3. Monatepil given orally (3–30 mg/kg) inhibited vasopressin (0.2 IU/kg, i.v.)‐induced ST depression which is considered to indicate ischaemic electrocardiographic changes in a vasospastic angina. This effect of monatepil was more potent and long‐lasting than that of diltiazem, and was similar to that of verapamil and nicardipine. At a dose of 30 mg/kg, monatepil produced a significant inhibition, even at 7 h after administration.4. Monatepil given intravenously (0.3 mg/kg) exerted a significant inhibitory effect on methacholine (16 μg/kg, intracoronary arterial administration; i.c.a.)‐induced ST elevation which seems to be caused by coronary vasospasm. This effect was more potent or equipotent to those of the existing calcium antagonists.5. These results indicate that monatepil produces the preventive effect on the drug‐induced ischaemic electrocardiographic changes in rats and suggest that monatepil may have potential for the treatmen

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01651.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. The effects of CGS 22652, a thromboxane (Tx) A2synthase inhibitor and TxA2prostaglandin (PG) H2 receptor antagonist, on blood pressure (BP) were studied in conscious freely moving spontaneously hypertensive rats (SHR).2. Three groups of 13 male SHR were subcutaneously infused from 5 to 11 weeks of age via osmotic minipumps with CGS 22652 at doses of 5 (SHRa) or 10 (SHRb) mg/ kg per 24 h or with the vehicle only (SHRc). A fourth group (SHRd,n= 13) was orally treated from 3 to 11 weeks of age with CGS 22652 (30 mg/kg) given by gavage once a day.3. CGS 22652 dose‐dependently reduced the age‐related increase in systolic BP. The pressor response to noradrenaline (200 ng/kg, i.v.) but not to angiotensin I or II was slightly (P<0.05) diminished in 11 week old SHRb and SHRd compared to SHRc. Acute ganglionic blockade by trimethaphan (10 mg/kg, i.v.), as well as angiotensin converting enzyme inhibition by perindopril (2 mg/kg, i.v.) decreased BP to a similar extent in the four groups. After combined blockade of vasopressin receptors and of the autonomic nervous system and the administration of a direct vasodilator (hydralazine, 3 mg/kg, i.v.), the residual mean BP was identical in the four groups of rats.4. Chronic treatment with CGS 22652 dose‐dependently antagonized the TxA2PGH2receptors but did not modify the TxA2synthesis. The urinary sodium excretion did not differ between groups.5. In conclusion, at the doses used, CGS 22652 given either orally or subcutaneously exhibited only TxA2/PGH2receptor blocking properties in SHR. Chronic treatment modestly prevented the development of hypertension in SHR, probably through a decrease in the pressor effects of TxA2and of noradren

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01652.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. The relationship between work‐rate and the antihypertensive effect of exercise in hypertensives, and the mechanism of that effect, were investigated by a crossover clinical trial.2. Ten mild hypertensives were randomly divided into two groups. One group performed low work‐rate exercise (LWE) on a cycle ergometer for 10 weeks (blood lactate threshold; ∼50% of maximum oxygen consumption [V̇O2max]). After a 10 week interval without exercise training, these subjects were then switched to a high work‐rate exercise (HWE) regimen (4 mmol/ L of blood lactate; ∼75% of V̇O2max) for another 10 weeks. In the other group, the order of exercise training was reversed. Since two patients withdrew from the protocol during HWE periods, statistical analysis was performed on the data from the remaining eight patients. There were no order effects observed in any of the data from the two groups.3. During both LWE and HWE, resting blood pressure (BP) fell significantly after the initiation of exercise therapy (P<0.05). Furthermore, the overall effects of 10 weeks of LWE and HWE on BP were not significantly different.4. The work‐rate at the lactate threshold, which reflects physical fitness, had increased significantly by 16 W (P<0.01) after the LWE period and by 11 W (P<0.01) after the HWE.5. During the LWE period, changes in haemodynamic and humoral variables were not significant, except for a reduction in plasma norepinephrine at week 10 (P<0.05). In the HWE period, changes in haemodynamic and humoral variables were not significant.6. Based on these findings, LWE is recommended for mild hypertensives because

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01653.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. The tetrabrominated diphenyl ether 3,5‐dibromo‐2‐(2,4‐dibromophenoxy)phenol (BPE), a natural marine product isolated from a sponge, was tested for pharmacological activity in guinea‐pig ileum.2. BPE (2 μmol/ L) decreased basal force and the frequency of spontaneous contractions of the ileum. It also significantly decreased contractions of the ileum induced by 5 mmol/L barium and to electrical stimulation at parameters which stimulated intrinsic nerves.3. The slopes of concentration‐response curves to acetylcholine (ACh), histamine and 5‐hydroxytryptamine (5‐HT) were significantly reduced by BPE at concentrations of 2 μmol/L or greater.4. BPE (2 μmol/L) did not affect calcium‐induced contractions of longitudinal muscle fibres from guinea‐pig ileum which were stripped of their cellular membrane. It (6 μmol/L) also had no effect on ATP levels in longitudinal muscle fibres.5. BPE (2 μmol/L) reduced both phasic and tonic components of contractions induced by raising the extracellular concentration of K+to 15, 30, 45 or 60 mmol/ L (in the presence of atropine, propranolol, phentolamine and desensitization to 5‐HT to inhibit the effects of nerve transmitter release).6. BPE (2 μmol/L) reduced carbachol‐induced contractions of ileum pre‐incubated in 1 μmol/L felodipine, a blocker of l‐type voltage‐operated calcium channels (VOCC).7. BPE dose dependently (0.6–6 μmol/L) reduced contractions induced by Ca2+in both K+depolarized ileum and in tissue exposed to carbachol (10 μmol/L) in the presence of felodipine (0.1 μmol/L).8. These results suggest that BPE affects intracellular messenger systems controlling cytosolic calcium and/or blocks entry of calcium into the cell through both

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01654.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. The aim of these experiments was to determine if the vasorelaxation of the rat isolated aorta induced by sufentanil or alfentanil is mediated by the endothelium, and, if not, by α‐adrenoceptor blockade, or a direct effect on the smooth muscle.2. Both sufentanil (from 10−7mol/L to 10−4mol/ L) and alfentanil (from 10−7mol/ L to 3 × 10−4mol/L) relaxed rings, where endothelium was intact and precontracted with 40 mmol/L KC1, in a concentration‐related manner. Similarly, sufentanil and alfentanil relaxed rings, in the presence or absence of endothelium, which had been precontracted with phenylephrine.3. Naloxone (10−4mol/L) had no significant effect on the relaxation induced by either sufentanil or alfentanil.4. In a similar manner as phentolamine, pretreatment with sufentanil protected α‐adrenoceptors from blockade by phenoxybenzamine (PBZ) in both endothelium intact and denuded rings, but the estimated potency of sufentanil was approximately 100‐fold less than that of phentolamine in α‐adrenoceptor protection. Treatment with alfentanil did not produce any receptor protection.5. We concluded that, in the rat aorta, vascular relaxation induced by sufentanil is mediated by both α‐adrenoceptor blockade and a direct effect on smooth muscle, whilst the relaxant effect of alfentanil is caused by direct effects alone. We also concluded that the endothelium has little role in relaxati

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01655.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. The effect of octopamine on the release of endogenous acetylcholine (ACh) from isolated ileal synaptosomal preparations of guinea‐pigs was examined using high pressure liquid chromatography with electrochemical detection. Release of ACh was induced by substance P or by depolarization with high potassium (50 mmol/ L) in medium containing atropine, propranolol and naloxone.2. Octopamine produced a dose‐dependent inhibition of substance P‐induced ACh release. A simiiar inhibitory action of octopamine was found in the samples depolarized by high potassium as a reference.3. The action of octopamine was not reversed by the dopamine receptor antagonists either for the DA‐2 subtype, domperidone, or for the DA‐1 subtype, SCH23390, or by haloperidol. However, idazoxan and yohimbine antagonized this octopamine‐induced inhibition at concentrations sufficient to abolish the action of clonidine.4. Failure of guanethidine or nomifensine to inhibit octopamine ruled out mediation by noradrenergic neurotransmitters.5. Octopamine decreased the influx of [45Ca] stimulated by substance P into synaptosomal preparations and this was reversed by idazoxan or yohimbine at concentrations sufficient to block the action of clonidine.6. Pertussis toxin abolished the inhibitory action of octopamine at a dose high enough to block the action of clonidine.7. These results indicate that octopamine suppresses the influx of calcium ions into cholinergic nerve terminals of ileal synaptosomes of guinea‐pigs via an activation of α2‐adrenoceptors coupled with a pertussis toxin‐sensitive GTP‐binding protein which results in a dec

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01656.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. The influence of perfusion pressure on flow distribution in the left ventricular wall was investigated with a newly developed microsphere method in Langendorff preparations of the rat heart.2. Microspheres with a diameter of 10 μm stained with the fluorescent dye yellow‐green were infused into the perfusion medium. The hearts were then relaxed with a calcium‐chelator, fixed with formaldehyde and cut transversally with a freezing microtome. Photographs were taken of the 52 μm slices with a fluorescence photomacroscope. The ventricular wall was subdivided into four zones, evaluated planimetrically and the beads were counted for calculation of microsphere density.3. Perfusion of groups of hearts, paced at 5 Hz, with Tyrode's solution at pressures of 30, 50, 80 or 120 cmH2O for 30 min revealed an increase of left ventricular pressure amplitude, coronary flow, myocardial oxygen consumption and flow redistribution towards the endocardium of the left ventricular wall with increasing perfusion pressure.4. The quotient of the sphere densities in the inner endocardium over that in the outer epicardium, however, was already maximal at a pressure of 80 cmH2O and amounted to 1.59 ± 0.15. This quotient was only 0.52 ± 0.11 at a perfusion pressure of 30 cmH2O, thus indicating massive change in flow distribution upon hypoperfusion.5. These results indicate that transmural left ventricular flow redistribution in response to hypoperfusion in the isolated rat heart is similar to that in hearts of much larger

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01657.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. The applicability of current indirect calorimetry formulae to the study of energy and substrate balances on obese rats has been evaluated. The energy consumption of series of 60‐day rats of Wistar, lean and obese Zucker stock were studied by means of direct and indirect calorimetry, and by establishing their energy balance through measurement of food intake and retention. Calorimetric studies encompassed a 24 h period, with gas and heat output measurements every 2 or 5 min, respectively, for direct and indirect calorimetry.2. The analysis of fat composition (diet, whole rat, and synthesized and oxidized fat) showed only small variations that had only a limited effect on the overall energy equation parameters.3. A gap in the nitrogen balance, which represents a urinary N excretion lower than the actual protein oxidized, resulted in significant deviations in the estimation of carbohydrate and lipid oxidized when using the equations currently available for indirect calorimetry.4. Analysis of the amino acid composition of diet and rat protein as well as of the portion actually oxidized, and correcting for the nitrogen gap allowed the establishment of a set of equations that gave better coincidence of the calculated data with the measured substrate balance.5. The measured heat output of all rats was lower than the estimated values calculated by means of either indirect calorimetry or direct energy balance measurement; the difference corresponded to the energy lost in water evaporation, and was in the range of one‐fifth of total energy produced in the three rat stocks.6. Wistar rats showed a biphasic circadian rhythm of substrate utilization, with alternate lipid synthesis/ degradation that reversed that of carbohydrate, concordant with nocturnal feeding habits. Zucker rats did not show this rhythm; obese rats synthesized large amounts of fat during most of the light period, consuming fat at the end of the dark period, which suggests more diurnal feeding habits. Lean Zucker rats showed a similar, but less marked pattern.7. The results obtained indicate that lean and obese rats can be studied using the same indirect calorimetry formulae provided that there is an adequate measure of protein oxidation and the composition of diet does not dif

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01658.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01659.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY