PT  - JOURNAL ARTICLE
AU  - Horacio Vidrio
AU  - Martha Medina
AU  - Pilar González-Romo
AU  - Marte Lorenzana-Jiménez
AU  - Patricia Díaz-Arista
AU  - Alejandro Baeza
TI  - Semicarbazide-Sensitive Amine Oxidase Substrates Potentiate Hydralazine Hypotension: Possible Role of Hydrogen Peroxide
AID  - 10.1124/jpet.103.055350
DP  - 2003 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 497--504
VI  - 307
IP  - 2
4099  - http://jpet.aspetjournals.org/content/307/2/497.short
4100  - http://jpet.aspetjournals.org/content/307/2/497.full
SO  - J Pharmacol Exp Ther2003 Nov 01; 307
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics