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  • 3H-digitoxin  (1)
  • Absorption  (1)
  • Endothelium-dependent relaxation  (1)
  • 1
    ISSN: 1432-1912
    Schlagwort(e): Key words SHR ; Endothelium-dependent relaxation ; Rat mesenteric vascular bed ; Rat thoracic aorta ; Bradykinin Acetylcholine ; Age dependency
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The present study examined whether alterations of endothelium-dependent vasorelaxation in spontaneously hypertensive rats (SHR) in response to the endothelium-dependent vasodilators acetylcholine and bradykinin ran parallel. We tried to find out the age at which endothelium-dependent vasorelaxation in response to each agonist became impaired and compared three different groups of SHR aged 7, 21 and 51 weeks. To be able to separate hypertension-induced alterations from age-dependent changes age-matched normotensive Wistar rats were included. Endothelium-dependent vasorelaxation was studied in the mesenteric vascular bed precontracted with noradrenaline, a typical resistance vessel, which showed relaxation to both acetylcholine and bradykinin, and the precontracted thoracic aorta, which only responded to acetylcholine. There were major differences in the agonist-dependent vasorelaxation between bradykinin and acetylcholine in SHR as a function of age. A surprising finding was that acetylcholine-induced relaxation was preserved, even slightly improved not only in young SHR (7 weeks) with developing hypertension but also in adult SHR (21 weeks) with established hypertension, which can be interpreted as a compensatory mechanism. As expected, in old SHR (51 weeks) acetylcholine-induced vasorelaxation was impaired as a consequence of the detrimental effects of long-term hypertension on endothelium. The parallel changes observed with acetylcholine in the mesenteric vascular bed and thoracic aorta provided mutual confirmation. In clear contrast to acetylcholine bradykinin-induced vasorelaxation was already impaired in young SHR with developing hypertension suggesting that bradykinin-induced vasorelaxation is either much more sensitive to detrimental effects of (even slightly) increased blood pressure or, more likely, that there is a basic deficiency in the action of bradykinin in SHR. Thus, our study allows to conclude that impairment of acetylcholine-induced endothelium-dependent vasorelaxation in the mesenteric vascular bed of SHR is a secondary phenomenon developing as a consequence of long-term hypertension while the impaired bradykinin-induced vasorelaxation seems to be a primary phenomenon that could be closely related to the development of hypertension.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 334 (1986), S. 496-500 
    ISSN: 1432-1912
    Schlagwort(e): k-Strophanthines ; Ouabain ; Absorption ; Metabolism ; Elimination ; Man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In 33 healthy male volunteers, given a single oral and intravenous dose of cymarin (k-strophanthin-α), k-strophanthoside (k-strophanthin-γ) and ouabain (g-strophanthin), enteral absorption and renal excretion of these glycosides and their metabolites were investigated by radioimmunoassay and HPLC. Cymarin was absorbed at 47% of the given dose. After intravenous injection 46% and after oral administration 21% of the given dose, i.e. the total amount as detected by radioimmunoassay which consisted of the unchanged glycoside and its metabolites, were excreted by the kidneys mainly as conjugated metabolites. The half-life of elimination, calculated from the total excreted amount was 13 h (i.v.) and 23 h (p.o.), respectively. k-Strophanthoside was absorbed at 16% of the given dose. After i.v.-injection 73% of the given dose was excreted by the kidneys with a half-life of elimination of 99 h. From this total amount about 70% was excreted as the unchanged drug, the remaining 30% as various metabolites. After oral administration 11% of the given dose were excreted with a half-life of elimination of 22 h. 80% of this amount consisted mainly of conjugated k-strophanthoside and conjugated metabolites as k-strophanthin-β, cymarin, k-strophanthidin, cymarol and k-strophanthidol. Only 6% was excreted as the unchanged drug. Ouabain was absorbed after oral administration to a minimum of 1.4%. Given intravenously a total renal excretion of 33% of the given dose with a half-life of elimination of 23 h was measured. Of this 80% was unchanged ouabain. The remaining 20% seemed to be conjugated metabolites which could not be exactly identified.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 9 (1976), S. 345-354 
    ISSN: 1432-1041
    Schlagwort(e): 3H-digitoxin ; metabolism ; spironolactone ; enzyme induction ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of spironolactone on the metabolism of intravenously administered3H-digitoxin (80 µCi) was investigated in eight patients. In three of them the labelled glycoside was given on a second occasion after spironolactone treatment had been discontinued for at least 65 days. Of total urinary radioactivity 79 % was unaltered drug and 12 % consisted of water soluble compounds. No digitoxigenin or digoxigenin and only trace amounts (〈2 %) of digoxin and the bis- and monoglycosides of digoxigenin were found. After spironolactone total urinary radioactivity was unchanged but the fraction eliminated as unchanged digitoxin fell from 79 to 66 % and the water soluble compounds increased from 12 to 26 % (p〈0.05). In addition spironolactone caused a 20 % reduction in the half-life of serum radioactivity (p〈0.01) and a 16 % reduction in the volume of distribution (p〈0.05). Induction of hepatic enzymes by spironolactone is proposed to explain the alteration in the metabolism of digitoxin in man. Both the altered metabolic pattern and the reduction in the volume of distribution appear to contribute to the reduction in half-life.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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