摘要:

SUMMARY1. The relaxing response of dopamine (DA) was studied in the rabbit pulmonary artery. DA caused concentration‐related relaxation in helically cut strips of the artery contracted with prostaglandin F2αin the presence of prazosin.2. The DA‐induced relaxation in endothelium‐denuded strips was reduced to about 40% compared with that in endothelium‐intact strips.3. Methylene blue and haemoglobin, inhibitors of endothelium‐dependent relaxation, reduced the DA‐induced relaxations in endothelium‐intact strips to the level of endothelium‐denuded strips. These results indicate that the DA‐induced relaxation is partially mediated or modified by the release of endothelium‐derived relaxing factor (EDRF).4. Apomorphine, as a DA agonist, caused concentration‐dependent relaxation in endothelium‐intact strips. Bromocriptine, a DA2 agonist, produced only a little relaxation at higher concentration.5. In endothelium‐intact strips, haloperidol, a DA antagonist, and the DA1antagonists, fluphenazine and SCH 23390 inhibited DA‐induced relaxations. On the other hand spiperone and domperidone, DA2 antagonists, were inactive.6. In endothelium‐denuded strips, fluphenazine and SCH 23390 inhibited DA‐induced relaxations, but domperidone was inactive.7. These results indicate that the DA‐induced relaxation is mediated by DA receptors, and that DA1receptors are involved in both endothelium‐dependent and‐independent rel

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00482.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. The effects of ranitidine on adrenergic transmission in the rat isolated anococcygeus muscle were investigated.2. Cumulative doses (2–8 mmol/ L) of ranitidine produced a concentration‐dependent inhibition of motor responses of the rat isolated anococcygeus muscle evoked by field stimulation (20–25 V, 10 Hz for 10 s, 1 ms pulse width) every 2 min, but also potentiated the contractile response to exogenous noradrenaline (5 μmol/L). The inhibited motor responses recovered rapidly and completely after washing out ranitidine.3. 4‐Aminopyridine (100 μmol/L) effectively reversed the partially inhibited (55% or greater) motor responses.4. The results strongly suggest that ranitidine can inhibit adrenergic transmission in the anococcygeus muscle by a prejunctional mechanism with, presumably, consequent development of supersensitivity of the effector cells to nora

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00483.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. Blood pressure (BP) declines dramatically in the final week of gestation in the pregnant spontaneously hypertensive rat (SHR). This study investigated the hypothesis that alterations of vascular neuroeffector function in the pregnant SHR and normotensive Wistar‐Kyoto (WKY) rat are responsible for this decline.2. Pregnancy in SHR and WKY rats was associated with a significant drop in BP in the last week of gestation.3. Responses of the perfused mesenteric vasculature to bolus doses of noradrenaline (NA) and potassium chloride (KC1) were decreased in preparations from SHR rats 4 days before delivery. This decreased responsiveness was absent in preparations from SHR rats 1 day before delivery. Responses of the perfused mesenteric vasculature to sympathetic nerve stimulation were not influenced by pregnancy in the SHR.4. It is concluded that while there are dynamic changes occurring in neurovascular function just prior to delivery, it is unlikely that they are wholly responsible for the dramatic decline in blood pressure in the SHR ra

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00484.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. The direct cardiac effects of angiotensin‐converting enzyme (ACE) inhibitor in 22 hypertensive patients were investigated. Radionuclide ventriculography and echocardiography were performed to measure left ventricular function before and 60 min after administration of a subdepressor dose of captopril.2. Since the response to ACE inhibitor is not uniform, patients were classified into 12 patients without significant blood pressure change following captopril (group I) and 10 patients with reduction of blood pressure (group II).3. Clinical and baseline haemodynamic characteristics were similar for the two groups.4. Ejection fraction (EF) increased without changes of heart rate and end‐diastolic dimension after ACE inhibitor in group I as well as group II. The change of EF was not different for the two groups. No correlation was found between changes in EF and blood pressure in group I patients.5. This study indicates that ACE inhibitor might directly influence left ventricular function independent of systemic haemodynamic chan

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00485.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. Becausein vitroadenylate cyclase activity studies suggest that parathyroid hormone (PTH) and calcitonin (CT) increase renal tubular calcium and magnesium reabsorption by stimulating the same transport mechanism, the separate and combined effects of these hormones on calcium and magnesium transport was assessed in the rat.2. Fractional excretion of calcium was 9.5 ±0.5% in calcium‐infused thyroparathyroidectomized (TPTX) rats and was reduced to 5.1 ±0.6 and 4.1 ±0.6% by maximal hypocalciuric concentrations of PTH and CT, respectively.3. Combined administration of maximal PTH and CT produced an effect on fractional and absolute calcium excretion similar to that recorded with maximal CT alone. The combined administration of half‐maximal concentrations of PTH and CT also produced a comparable fall in the fractional excretion of calcium to 3.0 ± 0.7%, which was similar to that observed in the ‘maximal CT’ and ‘maximal PTH plus CT’ groups. The magnesium reabsorption data were comparable.4. These results support biochemical data suggesting that PTH and CT act upon the same transport site, presumably within the thick ascending limb of Henle's loop, to facilitate calcium and magnesi

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00486.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. Serum, tissue and urine angiotensin I‐converting enzyme (ACE) activity was estimated in the following groups of rats: saline‐injected rats (controls); captopril‐treated (CAP) control animals (CONTROL‐CAP); puromycin aminonucleoside (PAN)‐induced nephrotic syndrome (NS); and CAP‐treated animals with NS (NS‐CAP).2. Serum ACE activity increased in the CONTROL‐CAP, NS, and NS‐CAP groups. The increase in the NS‐CAP group was significantly higher compared with the NS or CONTROL‐CAP groups.3. In the CONTROL‐CAP group, tissue ACE decreased in brain, heart and adrenal glands, and remained unchanged in the lung, testis, kidney, small intestine and liver. In the NS group, tissue ACE activity increased in the lung and testis, decreased in the brain and heart, and remained unchanged in the small intestine, adrenal glands, kidney and liver. Tissue ACE activity increased significantly in the NS‐CAP group compared with the other groups. This increase in tissue ACE may contribute to an increase in the serum ACE activity in the NS‐CAP group compared with the NS group.4. Urine ACE activity increased in the NS and NS‐CAP groups, although the rise in the NS‐CAP group was significantly higher. The urine ACE correlated significantly with the circulating levels of this enzyme in the NS and NS‐CAP groups. The loss of ACE in the urine in the presence of an increased serum ACE activity indicates that the biosynthesis of tissue ACE and its release into

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00487.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. Thein vitrobiological activities and the effect of protein binding on the relaxant effectsin vivoofN‐3‐alkylxanthine andN‐3‐alkyl‐N‐1‐methylxanthine derivative were investigated in guinea‐pigs.2. A significantly positive correlation was observed among thein vitromuscle relaxant activity, the cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE) inhibitory activity and the protein‐binding potency of xanthine derivatives. However, there was a weak relationship between these activities and affinity for adenosine receptors.3. When theophylline, enprofylline and 1‐methyl‐3‐propylxanthine (MPX) were injected intravenously in guinea‐pigs, their ED50 values were 6.1, 3.3 and 1.0 mg/kg, respectively. Plasma concentrations of these drugs obtained following the intravenous injection of the ED50 approximated the theoretically effective concentration (EC50) predicted from both the relaxant effectsin vitroand the protein binding parameters. A good linear correlation was observed between bodyweight in four species (rats, guinea‐pigs, rabbits and humans) and certain pharmacokinetic parameters of enprofylline and theophylline.4. The present study indicates that differences in the relaxant effects of these drugsin vitroandin vivocan be explained in part by protein binding, and that the protein binding of these xanthine bronchodilators is an important determinant for their pharmacological activity. Guinea‐pigs provide a useful model for studying pharmacodynamic‐pharmacokinetic relat

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00488.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. The effects of 14 lignocaine homologues on the maximum upstroke velocity (Vmax) of the action potentials (AP) were studied in guinea‐pig papillary muscles. These drugs possess one, two or three methyl groups in different positions: an ortho‐chloro,‐carbomethoxy or‐ethyl group instead of an ortho‐methyl group; or anN‐butyl group instead of anN‐diethyl group in lignocaine molecules.2. At 50–100 μol/L, six drugs possessing two ortho substituents (but not the other eight) reducedVmaxmore prominently at 2‐4 Hz than at 1 Hz, and slowed the time courses of recovery of the premature responses. None of the drugs affected resting potential.3. Besides the two‐state piecewise exponential model (models I and II) frequently used, a time‐dependent and time‐independent, two‐state model (model III) was formulated and applied to these experimental data. The above two groups were effectively distinguished by the difference of the estimated association and dissociation rate constants (model II) and equilibrium constants for phasic state (model III) and for resting (model II) or tonic (model III) states.4. The equilibrium constants for resting or tonic state correlated well with log P (where P = then‐octanol: water partition coefficients), but correlated better with an indicator variable that denotes the existence of two ortho substituents, suggesting the importance of the contribution of st

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00489.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00490.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00491.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY