In vitro and in vivo studies on the selectivity of beta-adrenoceptor antagonist drugs in the guinea-pig

1985 ◽  
Author(s):  
Karin Walduck
Keyword(s):  
Guinea Pig ◽  
In Vivo Studies ◽  
Beta Adrenoceptor ◽  
Adrenoceptor Antagonist

Systemic α1A-adrenoceptor antagonist inhibits neointimal growth after balloon injury of rat carotid artery

2003 ◽  
Vol 284 (1) ◽  
pp. H385-H392 ◽  
Author(s):  
John C. Teeters ◽  
Cauveh Erami ◽  
Hua Zhang ◽  
James E. Faber
Keyword(s):  
Vascular Disease ◽  
In Vivo Studies ◽  
The Novel ◽  
Balloon Injury ◽  
Systemic Hemodynamic ◽  
Adrenoceptor Antagonist ◽  
And Migration ◽  
Wall Injury

Previous in vitro and in vivo studies have shown that norepinephrine, acting through α1A-adrenoceptors, stimulates hypertrophy, proliferation, and migration of vascular smooth muscle cells and adventitial fibroblasts and may contribute to neointimal growth, lumen loss, and inward remodeling caused by iatrogenic wall injury and vascular disease. Our present aim was to determine whether intravenous administration of the α1A-adrenoceptor antagonist KMD-3213, at dosages without systemic hemodynamic effects, inhibits wall growth after injury. Inhibition of α1A-adrenoceptors with 12.8 and 32 μg/kg KMD-3213 had no effect on arterial pressure or renal and hindquarter resistances in anesthetized rats. A second group then received carotid balloon injury and continuous intravenous KMD-3213 at 4 and 10 μg · kg−1 · h−1for 2 wk. Mean, systolic, and diastolic arterial pressures and heart rate of conscious unrestrained rats were unaffected. KMD-3213 reduced neointima growth by ∼30 and 46% at the two doses ( P< 0.01). These data support the novel hypothesis that a direct α1A-adrenoceptor-dependent trophic action of catecholamines is augmented by injury and may contribute significantly to hypertrophic vascular disease.

Species differences in the reactivation of organophosphate-inhibited plasma esterases by diacetymonoxime

1976 ◽  
Vol 54 (2) ◽  
pp. 86-92 ◽  
Author(s):  
D. J. Ecobichon
Keyword(s):  
Guinea Pig ◽  
Species Differences ◽  
Marked Effect ◽  
Lethal Dose ◽  
Rat Plasma ◽  
In Vivo Studies ◽  
Rapid Rate ◽  
Plasma Enzymes

A study was conducted to assess whether the protection afforded to organophosphate-poisoned animals by diacetylmonoxime (DAM) was correlated with the reactivation of non-essential aliesterases (AliE). In vitro, the DAM-catalyzed reactivation of plasma AliE and cholinesterases (ΨChE) of rat, rabbit and guinea pig inhibited by 10−5 M diisopropylphosphorofluoridate (DFP) and O,O-dimethyl-2,2-dichlorovinyl phosphate (DDVP) was investigated. Marked reactivation of the rat plasma enzymes was achieved with 10 mM DAM. Higher concentrations (30 mM) were necessary for the slow reactivation of rabbit and guinea pig plasma AliE. Reactivation of the ΨChE of these species was comparatively slow. Reactivation of DDVP-inhibited esterases proceeded in all species at a more rapid rate than those inhibited by DFP. The dependence of ΨChE reactivation upon concomitant more rapid reactivation of AliE by DAM was demonstrated using Sephadex fractionated AliE and ΨChE but only a marked effect was observed with the rat, suggesting that the plasma AliE of this species is functionally different.The in vitro observations were confirmed by in vivo studies in rats and rabbits. DAM (50 or 150 mg/kg), administered to atropinized rats 15 min before a lethal dose of DFP, protected the animals. Few severe toxic signs were observed and reactivation of both plasma AliE and ΨChE occurred. In contrast, DAM protected the rabbit against a lethal dose of DFP but only reactivation of the erythrocyte acetylcholinesterase was observed.

scholarly journals Altered Contractile Response due to Increased β3-Adrenoceptor Stimulation in Diabetic Cardiomyopathy

2007 ◽  
Vol 107 (3) ◽  
pp. 452-460 ◽  
Author(s):  
Julien Amour ◽  
Xavier Loyer ◽  
Morgan Le Guen ◽  
Nejma Mabrouk ◽  
Jean-Stéphane David ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Diabetic Cardiomyopathy ◽  
Positive Inotropic Effect ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Inotropic Response ◽  
Beta Adrenoceptor ◽  
Adrenoceptor Antagonist

Background In the diabetic heart, the positive inotropic response to beta-adrenoceptor stimulation is altered and beta1 and beta2 adrenoceptors are down-regulated, whereas beta3 adrenoceptor is up-regulated. In heart failure, beta3-adrenoceptor stimulation induces a negative inotropic effect that results from endothelial nitric oxide synthase (NOS3)-derived nitric oxide production. The objective of our study was to investigate the role of beta3-adrenoceptor in diabetic cardiomyopathy. Methods beta-Adrenergic responses were investigated in vivo (dobutamine echocardiography) and in vitro (left ventricular papillary muscle) in healthy and streptozotocin-induced diabetic rats. The effect of beta3-adrenoceptor inhibition on the inotropic response was studied in vitro. Immunoblots and NOS activities were performed in heart homogenates (electron paramagnetic resonance) and isolated cardiomyocytes. Data are mean percentage of baseline +/- SD. Results The impaired positive inotropic effect was confirmed in diabetes both in vivo (121 +/- 15% vs. 160 +/- 16%; P &lt; 0.05) and in vitro (112 +/- 5% vs. 179 +/- 15%; P &lt; 0.05). In healthy rat, the positive inotropic effect was not significantly modified in presence of beta3-adrenoceptor antagonist (174 +/- 20%), nonselective NOS inhibitor (N -nitro-l-arginine methylester [l-NAME]; 183 +/- 19%), or selective NOS1 inhibitor (vinyl-l-N-5-(1-imino-3-butenyl)-l-ornithine [l-VNIO]; 172 +/- 13%). In diabetes, in parallel with the increase in beta3-adrenoceptor protein expression, the positive inotropic effect was partially restored by beta3-adrenoceptor antagonist (137 +/- 8%; P &lt; 0.05), l-NAME (133 +/- 11%; P &lt; 0.05), or l-VNIO (130 +/- 13%; P &lt; 0.05). Nitric oxide was exclusively produced by NOS1 within diabetic cardiomyocytes. NOS2 and NOS3 proteins were undetectable. Conclusions beta3-Adrenoceptor is involved in altered positive inotropic response to beta-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by NOS1-derived nitric oxide in diabetic cardiomyocyte.

In vitro and in vivo studies on the metabolism of estrogens and their sulfates in guinea pigs

1977 ◽  
Vol 55 (4) ◽  
pp. 390-397 ◽  
Author(s):  
R. Hobkirk ◽  
D. J. Freeman ◽  
P. R. C. Harvey ◽  
Mona Nilsen ◽  
Barbara Jennings
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Mature Male ◽  
In Vivo Studies ◽  
Pig Liver ◽  
Male And Female ◽  
Estradiol 17Β ◽  
Guinea Pig Liver

Labelled estradiol-17β(E2) or estrone (E1), when incubated with guinea pig liver slices, is metabolized by two main pathways. Part of each substrate is converted to estrone-3-glucuronide and estradiol-3-glucuronide. A further part of each is metabolized to estradiol-3-sulfate (E23S) and estrone-3-sulfate (E13S), which are interconverted. The latter conjugate appears to be the substrate for a 16α-hydroxylase forming 16α-hydroxyestrone-3-sulfate (16αOHE13S). This, in turn, is further sulfurylated to yield 16α-hydroxyestrone-3,16-disulfate, accompanied by estriol-3,16-disulfate. A relatively small amount of tentatively identified '6-hydroxyestrone disulfate' accompanies these other two diconjugates. The guinea pig liver system suggests itself as a useful and relatively simple model for further study of 16α-hydroxylation of E13S. The use of the latter as a natural substrate in the system in vitro is supported by our observation that E13S and E23S are present in liver, kidney, blood, gallbladder bile, intestine, uterus, and placenta after injection of labelled E2 into mature male and female guinea pigs. Some evidence has been obtained for the disulfate fraction (above) in liver and bile after injection of labelled E1.

In vitro and in vivo studies of new cationic Zn(II)‐benzonaphthoporphyrazines as photosensitizers for PDT

2001 ◽  
Vol 5 (8) ◽  
pp. 645-651
Author(s):  
M. Peeva ◽  
M. Shopova ◽  
U. Michelsen ◽  
D. Wöhrle ◽  
G. Petrov ◽  
...  
Keyword(s):  
In Vivo Studies

Effect of caffeine on theophyliine on cerebral blood flow response to brain activation: In vitro and in vivo studies

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S198-S198
Author(s):  
Joseph R Meno ◽  
Thien-son K Nguyen ◽  
Elise M Jensen ◽  
G Alexander West ◽  
Leonid Groysman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Activation ◽  
In Vivo Studies ◽  
Blood Flow Response ◽  
Flow Response

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu
Keyword(s):  
Guinea Pig ◽  
Acetylsalicylic Acid ◽  
Guinea Pigs ◽  
Glass Bead ◽  
Animal Species ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

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