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At least 73 records · Page 4Linked to original sources
PubMed1981

Effect of beta-aminopropionitrile on the static elastic properties and blood pressure of spontaneously hypertensive rats.

The static elastic properties of the aorta ad systolic blood pressure in the caudal artery have been measured in 55 spontaneously hypertensive rats of the AS strain. Animals were divided into five groups and treated from the age of 4 to 12 weeks as follows: (1) 0.25 mm silver clip positioned around the right renal artery; (2) renal artery clipped as group (1) followed by daily injection of beta-aminopropionitrile fumarate (beta-APN); (3) daly injection of beta-APN without clipping; (4) daily injection of 0.09% saline; (5) untreated. Mean systolic blood pressures at 12 weeks of age were Group (1) 21.8; Group (2) 16.2; Group (3) 17.0; Group (4) 18.0; Group (5) 17.5 (units kPa). Thus, administration of beta-APN prevents the development of renal hypertension in clipped animals while producing no significant alteration in animals with intact renal arteries. At pressures within the physiological range the functional distensibility of all the treated animals was greater than that of the controls (pressure strain elastic modulus significantly lower). Similar changes were observed in the variation of structural distensibility (incremental elastic modulus) with pressure. At any level of total strain greater than 0.7 the incremental elastic modulus of both groups of animals treated with beta-APN was significantly less than control values. These observations are consistent with reports in the literature that administration of beta-APN causes a reduction in either the amount of cross-linked or normal scleroprotein in the aorta.

Aminopropionitrile↗
PubMed1983

The B-aminopropionitrile-fed turkey: a model for detecting potential drug action on arterial tissue.

Broad-breasted white male turkeys develop hypertension, tachycardia and aortic arteriosclerosis spontaneously by approximately 5 weeks of age. When fed B-aminopropionitrile (BAPN), aortic tensile strengths are lowered, and a high percentage of the turkeys die from aortic dissecting aneurysms. There are essentially no deaths from aneurysms when either dl-propranolol or reserpine is fed in concert with BAPN; practolol and soltalol partially protect the BAPN-fed turkey from lethal aneurysms while hydralazine and phenelzine sulphate potentiate mortality from aneurysms. Dl-propranolol decreases and reserpine increases dP/dtmax and both drugs lower arterial pressure and heart rate when fed with BAPN. Such diets also decrease the ultrastructural disarray of collagenous and elastic fibres in the media of the abdominal aorta that occurs from the feeding of BAPN and thereby raise aortic tensile strength. Sotalol and practolol when fed to BAPN-fed turkeys lower blood pressure and dP/dtmax, but neither drug affects aortic tensile strength and both counteract the deleterious effect of BAPN on the ultrastructure of collagenous and elastic fibres to a minor degree. Phenelzine sulphate does not affect arterial pressure while hydralazine reduces arterial pressure; both drugs decrease aortic tensile strength and increase the ultrastructural disruption of aortic elastin and collagen in the BAPN turkey. The results suggest that dl-propranolol, reserpine, phenelzine sulphate, and hydralazine have an action on aortic tissue and indicate the usefulness of the BAPN-fed turkey as a model for identifying potential drug effects on aortic elastin and collagen.

Aminopropionitrile↗
PubMed1997

In vitro measurement of orthodontic tooth movement in rats given beta-aminopropionitrile or hydrocortisone using a time-lapse videotape recorder.

In vitro tooth movement of rat molars in response to an orthodontic force was recorded using a time-lapse videotape recorder and analysed by a computer system. Rats received daily s.c. injections of beta-aminopropionitrile (BAPN, 300 mg/kg/day) or hydrocortisone (10 mg/kg/day) for a period of 7 days. After drug administration, the animals were killed and the mandibles dissected. The jaw was then held under a stereomicroscope with a haemostatic clamp and an elastic band was inserted between the first and second molars. The movements of reference points on the occlusal surfaces of the first and second molars were recorded for 20 hours using a time-lapse videotape recorder. Mesiolingual movement of the first molar and distobuccal movement of the second molar were observed. During the experimental period, the greatest amount of total tooth movement in the first and second molars was seen in the group pretreated with BAPN, less movement was observed in the control group, and the group pretreated with hydrocortisone exhibited the least amount of movement. The highest rates of tooth movement were observed during the initial hour in each of the groups, and decreased thereafter. The initial rates of movement were also greatest in the BAPN group, less in the control group, and least in the hydrocortisone group. These results indicate that treatment with BAPN accelerated experimental tooth movements in vitro and hydrocortisone treatment inhibited the movements, suggesting that, although a part of the tooth movement measured in this experiment was due to deformation of the alveolar bone, the mechanical properties of the periodontal ligament play an important role in the regulation of orthodontic tooth movement.

Alveolar Process↗
PubMed2000

Analysis of the combined osteolathyritic effects of beta-aminopropionitrile and diethyldithiocarbamate on xenopus development.

In order to examine the mechanistic basis between combined effects and mechanisms of action, two osteolathyrogens, beta-aminopropionitrile (betaAPN) and diethyldithiocarbamate (DTC), were tested together on Xenopus embryos. In a separate test, DTC was also tested with copper sulfate to determine the importance of copper in DTC-induced osteolathyrism. Frog embryos (Xenopus laevis) were exposed for 96 h, with daily solution removal and replacement. Preserved tadpoles were evaluated for osteolathyritic lesions. For the betaAPN:DTC test, a 1.2-factor matrix design was used, producing two single chemical and seven mixture-response curves. The chi(2) goodness-of-fit test was used to compare the experimental mixture-response curves with theoretical effects for two combined effects models, dose-addition and independence. All seven mixture curves were consistent with expected results for dose-addition, but the correlations were generally not high. For the DTC:copper test, the three mixture-response curves generated showed that added copper increased the DTC-alone EC(50), but there was no corresponding right shift at the top of the response curves, as observed previously with betaAPN and copper. In the betaAPN:DTC and DTC:copper tests, DTC alone showed a biphasic concentration-osteolathyrism curve, and the slope of the response curve for DTC alone in each test was statistically different than the slope for the betaAPN alone response curve. Taken together, the results suggest the potential for a second osteolathyritic effect of DTC that affected the combined toxicity enough to produce a dose-addition correlation without the chemicals necessarily having the same mechanism.

Aminopropionitrile↗
PubMed1972

Sotalol for the protection of turkeys from the development of -aminopropionitrile-induced aortic ruptures.

1. The influence of feeding 2 levels of sotalol on the incidence of beta-aminopropionitrile (BAPN)-induced aortic ruptures of immature turkeys was determined.2. Four of 22 turkeys fed 0.12% sotalol and 0.07% BAPN died of aortic ruptures, but 6 of 21 turkeys fed only BAPN died of the syndrome.3. Blood pressure, heart rate, aortic tensile strength, and aortic structure as seen by light- and electron-microscope were similar in turkeys fed BAPN alone or both BAPN and 0.12% sotalol concurrently.4. In a second experiment, 13 of 24 turkeys fed 0.7% BAPN alone died of aortic ruptures, but only 2 of 24 turkeys fed BAPN and 0.2% sotalol concurrently died of the disease.5. Aortic tensile strength was lower, heart rate was faster, alterations of aortic elastic fibres as seen by light- and electron-microscope were more severe, and aortic salt soluble collagen with a higher amino acid content was increased in turkeys fed only BAPN, as compared to turkeys fed both BAPN and 0.2% sotalol.

Aminopropionitrile↗
PubMed1976

Beta-aminopropionitrile as a radiation reaction preventive agent.

Beta-aminopropionitrile (BAPN), an inhibitor of collagen maturation, was tested as a radiation reaction preventive agent (RRPA) using radiation-induced lung fibrosis in rats and mice as a model. Following pulmonary irradiation, treatment with BAPN significantly prevented an increase in collagen content as measured by hydroxyproline analysis. This effect persisted during BAPN maintenance for periods of up to 10 weeks but was lost when the drug was discontinued. BAPN administration did not increase the mouse lung LD50/160 in the drug doses employed in this study. Other possible RRPAs deserving further study include D-penicillamine and beclomethasone dipropionate.

Aminopropionitrile↗
PubMed1984

Reduction of chronic hypoxic pulmonary hypertension in the rat by beta-aminopropionitrile.

We administered antifibrotic agent beta-aminopropionitrile (BAPN) to rats exposed to 10% O2-90% N2 for 3 wk to prevent excess vascular collagen accumulation. Groups of Sprague-Dawley rats studied were air breathing, hypoxic, and hypoxic treated with BAPN, 150 mg/kg twice daily intraperitoneally. After the 3-wk period, we measured mean right ventricular pressure (RVP), the ratio of weight of right ventricle to left ventricle plus septum (RV/LV + S), and hydroxyproline content of the main pulmonary artery (PA) trunk. Hypoxia increased RVP from 14 to 29 mmHg; RVP was 21 mmHg in hypoxic BAPN-treated animals. Hypoxia increased the RV/LV + S ratio from 0.28 to 0.41; the ratio was 0.32 in hypoxic BAPN-treated animals. Hypoxia increased PA hydroxyproline from 20 to 239 micrograms/artery; hydroxyproline was 179 micrograms/artery in hypoxic BAPN-treated animals. Thus BAPN prevented pulmonary hypertension, right ventricular hypertrophy, and excess vascular collagen produced by hypoxia. We conclude that vascular collagen contributes to the maintenance of chronic hypoxic pulmonary hypertension.

Aminopropionitrile↗
PubMed1982

Effect of hydralazine on aortic rupture induced by B-aminopropionitrile in turkeys.

The effects of hydralazine on aortic rupture, hemodynamics and aortic ultrastructure were studied in turkeys fed B-aminopropionitrile (BAPN). A mortality rate of 24% due to hemopericardium and internal hemorrhage in turkeys fed only BAPN increased to 91% when turkeys were fed both BAPN and hydralazine, despite a significant reduction in blood pressure after both drugs. Death rates among turkeys fed BAPN and hydralazine were lowered by adding either dietary propranolol (53%), which lowered blood pressure and dP/dt max, or reserpine (67%), which reduced blood pressure and increased dP/dt max. Striking ultrastructural alterations of collagenous and elastic fibers of the aortic media, which were additive to the effects of BAPN alone, were induced by BAPN and hydralazine. This study demonstrates that a 6-week feeding of high levels of BAPN and hydralazine, which accumulates in vessel walls, can produce vascular injury and increase mortality from hemorrhage in lathyritic turkeys.

Aminopropionitrile↗
PubMed1988

Nitrogen-dioxide-induced emphysema in rats. Lack of worsening by beta-aminopropionitrile treatment.

We evaluated the effect of beta-aminopropionitrile (beta APN) on the nitrogen dioxide (NO2) animal model of emphysema. Rats maintained on a beta APN-supplemented or a regular diet were exposed to 30 ppm NO2 for intervals ranging from 1 to 8 wk. Emphysema development was assessed by histologic evaluation and by changes in lung volume and mean linear intercept values. Evidence of pathologic changes were also documented by clinical and radiographic findings of osteolathyrism. The induction of centriacinar emphysema was attributed specifically to NO2 exposure. Neither the severity of the emphysema nor the time course of its development was altered by the beta APN-supplemented diet. These findings are in marked contrast to those observed with the exogenous elastase model of the disease, and they suggest that elastin synthesis and repair may not modulate elastin destruction in the NO2 model of emphysema.

Aminopropionitrile↗
PubMed1981

Lung lysyl oxidase and prolyl hydroxylase: increases induced by cadmium chloride inhalation and the effect of beta-aminopropionitrile in rats.

Industrial workers who are accidentally exposed to cadmium fumes often develop severe lung damage leading to widespread peribronchiolar scarring. This study examined the effect of a single exposure of cadmium chloride aerosol on rat lung lysyl oxidase and prolyl hydroxylase, both markers of connective tissue biosynthesis. Rats were killed at 2, 4, 7, 10, and 21 days after a 2-h exposure to 0.1% Cdcl2 aerosol. Total lung lysyl oxidase was increased 14.8 times that a saline control animals by 4 days and returned to near normal values by 10 days. Interestingly, a small amount of lysyl oxidase activity was also detectable in the lung lavage of unexposed animals and was markedly elevated at the earlier times after cadmium exposure. Total lung prolyl hydroxylase activity paralleled that of lung lysyl oxidase and increased 7.4-fold by the fourth day. A significant increase in total lung hydroxyproline could be demonstrated. Administration of beta-aminopropionitrile, an irreversible inhibitor of lysyl oxidase, prevented much of the increase in lysyl oxidase activity and the accumulation of collagen. The altered tissue amounts of lysyl oxidase and prolyl hydroxylase after cadmium inhalation correlated well with the marked interstitial cell hyperplasia 4 to 5 days after exposure and suggested that connective tissue protein synthesis is activated in the interstitial cell fibroblasts soon after cadmium exposure.

Aerosols↗
PubMed1982

beta-Aminopropionitrile prevents bleomycin-induced pulmonary fibrosis in the hamster.

beta-Aminopropionitrile (beta APN), an agent that prevents collagen accumulation in tissues, was evaluated for its ability to prevent excess collagen formation in bleomycin-induced pulmonary fibrosis in the hamster. Two groups of animals received a single endotracheal dose of bleomycin; one of these was injected with beta APN twice daily for 30 days. A third group received endotracheal saline and a fourth group received saline and beta APN. After 30 days, we measured pressure-volume curves of saline-filled lungs, collagen content, and degree of fibrosis. Endotracheal bleomycin increased collagen content, decreased lung volume, and produced fibrosis and a mortality rate of 51%. The administration of beta APN to bleomycin-treated animals prevented excess collagen accumulation and diminished total protein, reversed volume diminution, produced less fibrosis, and improved the mortality rate to 24%; beta APN alone had no effect on lung mechanics or collagen content. The biochemical, functional, and structural features of bleomycin-induced lung fibrosis are amenable to control with beta APN.

Aminopropionitrile↗
PubMed1982

The effect of oxygen on Cor pulmonale in experimental emphysema induced by elastase or elastase and beta-aminopropionitrile in hamsters.

Right ventricular hypertrophy in elastase-induced emphysema in the System hamster was assessed by either the weight of the right ventricle as a fraction of body-weight or by the ratio of the weight of the right to the left ventricle. Right ventricular hypertrophy accompanies elastase-induced emphysema and is more severe in hamsters injected with elastase while fed a diet containing 0.5% beta-aminopropionitrile (BAPN), a combination that causes more severe emphysema. Measurements of arterial blood oxygen pressures showed that emphysematous animals were hypoxemic. Treatment of emphysematous animals with 35% O2 either during the development of right ventricular hypertrophy or after it had developed produced measurable amelioration of the hypertrophy in those groups with the more severe emphysema (elastase plus BAPN diet) but did not completely prevent it. The oxygen had no effect on the severity of the emphysema measured morphometrically. These results indicate that the cor pulmonale in elastase-induced emphysema is probably multifactorial, but hypoxia appears to be one of the major factors.

Aminopropionitrile↗
PubMed1994

Modulation by beta-aminopropionitrile of vessel luminal narrowing and structural abnormalities in arterial wall collagen in a rabbit model of conventional balloon angioplasty versus laser balloon angioplasty.

This study was designed to assess the potential relationship between the late loss of angiographic luminal diameter and biochemical abnormalities of arterial wall collagen in rabbits subjected to angioplasty, and to test the hypothesis that beta-aminopropionitrile (beta APN), an inhibitor of lysyl oxidase, would inhibit such changes when administered orally for 1 mo after angioplasty. Endovascular injury was induced in rabbit iliac arteries by ipsilateral balloon angioplasty (BA) and by contralateral balloon angioplasty accompanied by exposure to continuous wave neodymium: yttrium aluminum garnet laser radiation (LBA). Computer measurement of angiographic luminal diameter demonstrated significant vessel narrowing at 1 and 6 mo after both procedures. By quantitative histology, the majority of the 1-mo loss in angiographic diameter could not be attributed to neointimal thickening. Analysis of collagen cross-linking by HPLC in collagen obtained from the LBA-injured segments of the arteries 1 mo after angioplasty revealed a significant increase, relative to values from uninjured arteries (P < 0.05), in the difunctional cross-link dihydroxylysinonorleucine (DHLNL). 6 mo after angioplasty, the content of hydroxypyridinium, the trifunctional maturational product of DHLNL, was significantly elevated in both BA- and LBA-treated arteries compared with values from uninjured arteries (P < 0.05). In animals administered beta APN, luminal narrowing at 1 mo, compared with controls, was attenuated (P < 0.01) and DHLNL content was decreased (P < 0.05) in arteries subjected to LBA, but not in arteries subjected to BA. The results suggest that lathyrogenic agents may be efficacious in favorably modulating LBA-induced alterations in vessel diameter and mural connective tissue.

Aminopropionitrile↗
PubMed1977

Increased lysyl oxidase activity in blood vessels of hypertensive rats and effect of beta-aminopropionitrile on arteriosclerosis.

The activity of lysyl oxidase which catalyzes the initial step of cross-linking of collagen and elastin polypeptides was measured in blood vessels of the hypertensive rat. The enzyme activity was increased in the aorta and mesenteric artery when hypertension was induced in 8-week-old rats with administration of deoxycorticosterone acetate (DOCA) and 1% saline. Reserpine diminished this increase in vascular lysyl oxidase activity concomitant with reduction in blood pressure. When beta-aminopropionitrile, a specific inhibitor of lysyl oxidase, was administered before the onset of DOCA-salt hypertension, the aortic collagen content was reduced markedly. Concomitant with reduction in the aortic collagen content, the development of hypertension and arteriosclerotic changes in the kidney was partially prevented. These results would indicate that hypertension increases the amount and the degree of cross-linking of vascular collagen and that the deposition of excess collagen in the vascular wall contributes to the development of hypertension and arteriosclerosis.

Amino Acid Oxidoreductases↗
PubMed1990

Atherosclerosis mouse model induced by a high-cholesterol diet supplemented with beta-aminopropionitrile: effects of various anti-atherosclerotic agents on the biochemical parameters.

A mouse model of atherosclerosis was produced by feeding a 1.5% cholesterol diet with 0.4% beta-aminopropionitrile (BAPN) fumarate, a chemical lathyrogen, for 10 weeks, and the pharmacological sensitivity and specificity of this model were evaluated biochemically with various hypolipidemic drugs and calcium antagonists. Histological findings on this model showed typical angiolathyrism with foam cells in the media of the thoracic aorta. Uniform and marked accumulation of cholesterol, notably esterified cholesterol, in the aorta was observed, although it was much less in mice receiving a high-cholesterol diet or BAPN alone. The reduction in elastin contents in the aorta was a characteristic feature of this model. Clofibrate, cetaben and elastase tended to prevent the increase of cholesterol contents in the aorta, together with their significant hypocholesterolemic effects. Nifedipine, diltiazem and verapamil showed a slight preventive effect on the cholesterol accumulation and on the reduction of elastin content in the aorta without a cholesterol lowering effect in the serum. MgCl2 was more effective than other calcium antagonists and even had a hypocholesterolemic effect. The results indicate that this mouse atherosclerosis model may be usable for primary drug evaluation.

4-Aminobenzoic Acid↗
PubMed1980

Increased collagen cross-linkages in experimental diabetes: reversal by beta-aminopropionitrile and D-penicillamine.

The effects of diabetes on collagen cross-link formation and solubility were investigated in granulation tissue collagen induced by polyester fabric implanted subcutaneously in rats at the same time diabetes was produced by injection of streptozotocin. Thus, all the collagen analyzed was formed in a diabetic milieu. Ten days later the implants were removed and the total collagen content as well as the fraction soluble in 0.5 M acetic acid was determined. Predominantly type I collagen accumulated in the implants. Total collagen content was the same in diabetics and controls; however, the acid-soluble fraction in diabetic animals was only half that of controls (8.5% and 17.7%, respectively), and the ratio of beta chains to alpha chains in the acid-soluble fraction was higher in diabetics (0.89) than in controls (0.69). In animals treated with beta-aminopropionitrile or D-penicillamine the acid-soluble fraction of collagen from diabetics equaled that from controls. These observations indicate that both intramolecular and intermolecular cross-links are increased in type I collagen from diabetic animals. Since these cross-links interfere with degradation of collagen by collagenase, they may contribute to accelerated intimal sclerosis of arteries and to capillary basement membrane thickening in diabetes.

Amino Acids↗
PubMed1999

Combined osteolathyric effects of beta-aminopropionitrile and penicillamine on Xenopus embryos: statistical comparison with dose-addition and independence.

The combined osteolathyric effects of beta-aminopropionitrile (beta APN) and penicillamine (PNC) on developing Xenopus embryos were determined and compared with theoretical effects for the dose-addition and independence models. The testing protocol utilized a 1.2-factor matrix design that generated two single chemical and seven mixture concentration-response curves within 36 treatments. Testing was for 96-h with daily solution removal and replacement. The chi 2 goodness-of-fit test was used to compare experimental responses with theoretical responses. Response curve analyses indicated, in general, a combined effect between that expected for dose-addition and that for independence, which is a combined effect typical of chemicals acting dissimilarly.

Aminopropionitrile↗
PubMed1985

Alterations of elastin fibrogenesis by inhibition of the formation of desmosine crosslinks. Comparison between the effect of beta-aminopropionitrile (beta-APN) and penicillamine.

Experimental lathyrism was induced by feeding newborn chicks a diet containing 0.2 and 0.4% DL-Penicillamine, with or without CuSO4 (10 mg/Kg diet) and Vitamin B6 (100 mg/Kg diet), or 0.015 and 0.1% beta-aminopropionitrile fumarate (beta-APN). After 7, 15, 25 and 55 days of treatment the animals were killed, the aortas removed and processed for electron microscopy in the presence of markers for proteoglycans, and the elastic fibers were carefully examined. Penicillamine, which prevents the formation of desmosine crosslinks by binding to precursors, induced the production of numerous new elastin fibers which appeared normal from the ultrastructural point of view. It seems, therefore, that at least in chick aortas, desmosine crosslinks are not necessary for the aggregation of tropoelastin molecules into structurally normal fibers. On the contrary, beta-APN, a classical inhibitor of lysyl oxidase, induced the tropoelastin molecules to aggregate into abnormal protuberances on the old fibers. Moreover, the elastin deposited during beta-APN treatment was always permeated by cytochemically revealed proteoglycans, which were never observed after penicillamine treatment. It is speculated that, at least in the system under study, the epsilon-amino groups of tropoelastin molecules may offer the binding sites for matrix proteoglycans until they are removed by lysyl oxidase, and that matrix proteoglycans might play a role in elastin fibrogenesis by preventing spontaneous tropoelastin aggregation in areas far from growing elastin fibers.

Amino Acids↗