Free radicals generated by xanthine/xanthine oxidase system augment nitric oxide synthase (NOS) and cyclooxygenase (COX)-independent component of bradykinin-induced vasodilatation in the isolated guinea pig heart.
Journal Title: Pharmacological Reports - Year 2006, Vol 58, Issue 3
Abstract
Recently, we have reported that bradykinin (Bk)-induced vasodilation was selectively potentiated by a low concentration of reactive oxygen species (ROS) generated by xanthine/xanthineoxidase system (XOX) in the coronary circulation of the isolated guinea pig heart. In an attempt to identify a mechanism of Bk response that is amplified by XOX, we analyze here the involvement of B1/ B2 receptors and the participation of NOS/COX pathways in the Bk responses before and after intracoronary infusion of XOX in the isolated guinea pig heart. Bk (0.3-3 pmoles) and acetylcholine (Ach) (100-300 pmoles) induced a dose-dependent coronary vasodilation. In the presence of a non-selective nitric oxide synthase (NOS) inhibitor L-NAME (10(-4) M) and non-selective cyclooxygenase inhibitor indomethacin (5 x 10(-3) M), vasodilation induced by Bk or Ach was inhibited. XOX infusion into the coronary circulation augmented Bk-induced vasodilation by approximately 100-300%. This effect was sustained and was observed at least 1h after XOX infusion. In contrast to Bk response, vasodilation induced by Ach was not modified by XOX infusion. Surprisingly, in the presence of L-NAME+indomethacin, Bk-induced response was still amplified by XOX. In relative terms, this effect was even more pronounced. Again, under these experimental conditions, the response to Ach remained largely unchanged. In the presence of B2 receptor antagonist, icatibant (100 nM), Ach-induced vasodilation was unaffected, while Bk-induced vasodilaton was abolished before and after XOX. In conclusion, in the isolated guinea pig heart low concentration of exogenous ROS generated by XOX system resulted in a sustained augmentation of Bk-induced coronary vasodilatation that cannot be explained by the up-regulation of B1 receptors, or the amplification of activity of NOS-cGMP or COX pathways. The chemical identity of NOS/COX-independent component of Bk response that is up-regulated by XOX remains to be determined. EDHF is the most likely candidate.
Authors and Affiliations
Valery Kozlovski, Rafał Olszanecki, Stefan Chlopicki
Keywords
Related Articles
- EP ID EP159822
- DOI -
- Views 87
- Downloads 0
Immobility stress induces depression-like behavior in the forced swim test in mice: effect of magnesium and imipramine.
Previously, we demonstrated antidepressant-like effect of magnesium (Mg) in the forced swim test (FST). Moreover, the joint administration of Mg and imipramine (IMI) at ineffective doses per se, resulted in a potent redu...
Different effects of postnatal caffeine treatment on two pentylenetetrazole-induced seizure models persist into adulthood.
Postnatal treatment with caffeine from P7 to P11 (10 or 20 mg/kg daily) resulted in transient changes in two pentylenetetrazole (PTZ)-induced models of epileptic seizures characterized by spike-and-wave EEG rhythm in imm...
Chemical structure of phenothiazines and their biological activity.
Phenothiazines belong to the oldest, synthetic antipsychotic drugs, which do not have their precursor in the world of natural compounds. Apart from their fundamental neuroleptic action connected with the dopaminergic rec...
Interactions between drugs and sulforaphane modulate the drug metabolism enzymatic system.
Background: Sulforaphane (SFN) is a potent chemopreventive agent, which is widely consumed in diet or as a diet supplement. It modulates the enzymes of II and III metabolism phase. In this paper, the influence of SFN and...
Non-competitive metabotropic glutamate subtype 5 receptor antagonist (SIB-1893) decreases body temperature in rats.
This study examined the effect of (E)-2-methyl-6-(2-phenylethynyl)-pyridine (SIB-1893), a selective non-competitive metabotropic glutamate subtype 5 receptor (mGluR(5)) antagonist, on body temperature in freely moving Wi...