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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Cardiovascular drug reviews 13 (1995), S. 0 
    ISSN: 1527-3466
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 359 (1999), S. 394-399 
    ISSN: 1432-1912
    Keywords: Key words Angiotensin II ; ACE inhibition ; Moexiprilat ; Enalaprilat ; Cardiac fibroblast ; Mitogen ; activated protein kinases (MAPKs) ; Signal transducer and activator of transcription (STAT)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the effects of angiotensin converting enzyme (ACE) inhibitors on angiotensin II (Ang II) induced growth related signalling pathways in neonatal rat cardiac fibroblasts. In BrdU proliferation assays, Ang II (10–9–10–7 M) stimulated cardiac fibroblast growth in a dose-dependent fashion (maximum at 10–7 M, 5.22 ± 0.01-fold, n = 9). 2-2-(1-(ethoxycarbonyl)-3-phenylpropyl)-[amino-oxopropyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3 carboxylic acid (moexiprilat) led to a dose-dependent inhibition of the Ang II induced cardiac fibroblast growth. A less pronounced effect on cellular proliferation was seen with the ACE inhibitor enalaprilat. To elucidate the mechanisms involved in this direct antiproliferative effect of ACE inhibitors in cardiac fibroblasts, we studied the activation of mitogen-activated protein kinases [MAPKs: extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38-MAPK] and JAK/STAT (janus kinases/signal transducer and activator of transcription) signal transduction pathways. Ang II (10–7 M) caused an increase in MAPKs activity with an increased phosphorylation of ERK1/2 (1.7-fold) and p38-MAPK (3.6-fold). This effect was completely inhibited by moexiprilat (10–7 M) and enalaprilat (10–7 M). Stimulation with Ang II (10–7 M) also led to an increased phosphorylation of STAT3, which is one of the key effector proteins in the JAK/STAT signalling pathway. This effect was also completely inhibited by moexiprilat (10–7 M) and enalaprilat (10–7 M). These data show that the ACE inhibitors moexiprilat and enalaprilat inhibit Ang II induced proliferation of cardiac fibroblasts according to their relative potency of ACE inhibition in vitro. This novel effect of ACE inhibitors is accompanied by blocking the Ang II induced activation of several intracellular signal transduction pathways (ERK1/2, p38-MAPK and STAT3).
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7241
    Keywords: female spontaneously hypertensive rats ; estrogens ; arterial stiffness
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of estrogen replacement therapy in menopausal women are more obvious on bones than on the cardiovascular system. The optimal estrogen dosage may differ in these different parts of the body. In hypertensive rats, low doses have been shown to reduce arterial collagen and stiffness, whereas higher dosages are required for osteoprotection. From 4 to 20 weeks of age, female spontaneously hypertensive rats (SHRs) were divided into four groups: without ovariectomy, under placebo or 17β-estradiol (10 μg/kg/day), and with ovariectomy under either placebo or 17β-estradiol (same dosage). Serial tail systolic blood pressure measurements were performed, and histomorphometry of the thoracic aorta was determined at the end of the study. Under estrogen, blood pressure was unchanged, whereas the aortic wall–to–lumen ratio was increased, particularly in the presence of ovariectomy. The elastin to collagen ratio was significantly decreased, due both to a decrease in elastin and an increase in collagen density, with no change in media thickness. The latter findings were not observed when ovariectomy was performed. Independent of changes in wall stress, high-dose estrogen increases the aortic extracellular matrix in female SHRs. This increase may be reversed in the presence of ovariectomy, suggesting that estrogen was not the only gonadal factor responsible for altered vascular structure and function.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7241
    Keywords: carotid–femoral pulse wave velocity ; arterial compliance ; moexipril ; HRT ; hormone replacement therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Menopause and essential hypertension are associated with a decreased compliance and distensibility of the arteries. ACE inhibitors have been shown to improve arterial distensibility. Hormone replacement therapy (HRT), especially estrogens, could have a positive influence through their atheroprotective, vasodilative, and blood pressure–lowering effect. The vascular interactions of HRT and ACE inhibitors, like moexipril hydrochloride, have not been investigated so far. This trial was intended to assess the effect of combined sequential HRT for 25 days on acute changes in arterial distensibility after a single oral dose of 15 mg moexipril hydrochloride in postmenopausal women with borderline to mild essential hypertension. This study had a monocentric, randomized, parallel-group design, and was open for moexipril, and double-blind, and placebo-controlled for HRT. Assessment of arterial distensibility was by automatic noninvasive measurement of the carotid–femoral pulse wave velocity (PWV). The PWV and the pulse pressure decreased significantly after a single oral dose of 15 mg moexipril. An influence of HRT on the changes in the PWV and pulse pressure could not be seen. The plasma concentrations of renin increased and of aldosterone decreased after moexipril administration. Arterial function improves after acute administration of 15 mg moexipril in postmenopausal women with mild to moderate essential hypertension. The changes in PWV and pulse pressure are of similar magnitude in women with and without HRT.
    Type of Medium: Electronic Resource
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