Semicarbazide-sensitive amine oxidase substrates potentiate hydralazine hypotension:: Possible role of hydrogen peroxide

被引:22
|
作者
Vidrio, H
Medina, M
González-Romo, P
Lorenzana-Jiménez, M
Díaz-Arista, P
Baeza, A
机构
[1] Univ Nacl Autonoma Mexico, Fac Med, Dept Pharmacol, Mexico City 04510, DF, Mexico
[2] Univ Nacl Autonoma Mexico, Fac Chem, Dept Analyt Chem, Mexico City 04510, DF, Mexico
来源
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS | 2003年 / 307卷 / 02期
关键词
D O I
10.1124/jpet.103.055350
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The relation between inhibition of semicarbazide-sensitive amine oxidase (SSAO) and vasodilation by hydralazine (HYD) was evaluated in chloralose/urethane-anesthetized rats pretreated with various substrates of the enzyme and subsequently administered a threshold hypotensive dose of the vasodilator. The SSAO substrates benzylamine, phenethylamine, and methylamine potentiate the hypotensive response to HYD. Methylamine, which was studied in greater detail because of its status as a possible endogenous SSAO substrate, does not influence the response to the reference vasodilator pinacidil; it does enhance HYD relaxation in aortic rings obtained from pretreated rats. Experiments designed to identify the product of SSAO activity responsible for potentiation by methylamine suggest involvement of hydrogen peroxide (H2O2), as evidenced by the findings that such potentiation is abolished by additional pretreatment with the H2O2-metabolizing enzyme catalase, and that the plasma concentration of H2O2 is increased by methylamine and decreased by HYD. These results are interpreted as a substantiation of the relation between the known SSAO inhibitory effect of HYD and its vasodilator activity. Pretreatment with the SSAO substrates would increase production of H2O2 in vascular smooth muscle and thus magnify the influence of this vasoconstrictor agent on vascular tone. In these conditions, the decrease in H2O2 production and hence in vascular tone caused by SSAO inhibition by HYD would also be magnified. It is speculated that inhibition of vascular SSAO could represent a novel mechanism of vasodilation.
引用
收藏
页码:497 / 504
页数:8
相关论文
共 50 条
  • [21] Semicarbazide-sensitive amine oxidase:: Current status and perspectives
    Mátyus, P
    Dajka-Halász, B
    Földi, A
    Haider, F
    Barlocco, D
    Magyar, K
    CURRENT MEDICINAL CHEMISTRY, 2004, 11 (10) : 1285 - 1298
  • [22] SEMICARBAZIDE-SENSITIVE AMINE OXIDASE ACTIVITY IN CATFISH TISSUES
    KUMAZAWA, T
    SENO, H
    SUZUKI, O
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY, 1989, 92 (02): : 347 - 349
  • [23] Overexpression of semicarbazide-sensitive amine oxidase in human myopathies
    Olivé, M
    Unzeta, M
    Moreno, D
    Ferrer, I
    MUSCLE & NERVE, 2004, 29 (02) : 261 - 266
  • [24] Semicarbazide-sensitive amine oxidase activity in the human heart
    Pino, R
    Mazzetti, L
    Buffoni, F
    MOLECULAR GENETICS AND METABOLISM, 1998, 64 (01) : 70 - 75
  • [25] Semicarbazide-sensitive amine oxidase (SSAO): present and future
    Kálmán Magyar
    Zsuzsa Mészáros
    InflammoPharmacology, 2003, 11 (2) : 165 - 173
  • [26] HYDRALAZINE IS AN IRREVERSIBLE INHIBITOR OF THE SEMICARBAZIDE-SENSITIVE, CLORGYLINE-RESISTANT AMINE OXIDASE IN RAT AORTA HOMOGENATES
    LYLES, GA
    CALLINGHAM, BA
    JOURNAL OF PHARMACY AND PHARMACOLOGY, 1982, 34 (02) : 139 - 140
  • [27] Serum level of semicarbazide-sensitive amine oxidase in children with ADHD
    Roessner V.
    Uebel H.
    Becker A.
    Beck G.
    Bleich S.
    Rothenberger A.
    Behavioral and Brain Functions, 2 (1)
  • [28] METHYLAMINE METABOLISM TO FORMALDEHYDE BY VASCULAR SEMICARBAZIDE-SENSITIVE AMINE OXIDASE
    BOOR, PJ
    TRENT, MB
    LYLES, GA
    TAO, M
    ANSARI, GAS
    TOXICOLOGY, 1992, 73 (03) : 251 - 258
  • [29] SEMICARBAZIDE-SENSITIVE AMINE OXIDASE ACTIVITY IN STREPTOZOTOCIN DIABETIC RATS
    HAYES, BE
    CLARKE, DE
    RESEARCH COMMUNICATIONS IN CHEMICAL PATHOLOGY AND PHARMACOLOGY, 1990, 69 (01): : 71 - 83
  • [30] SILICON-MEDIATED INACTIVATION OF SEMICARBAZIDE-SENSITIVE AMINE OXIDASE
    DANZIN, C
    COLLARD, JN
    MARCHAL, P
    SCHIRLIN, D
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1995, 5 (20) : 2363 - 2366