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Myeloperoxidase evokes substantial vasomotor responses in isolated skeletal muscle arterioles of the rat
Author(s) -
Csató V.,
Pető A.,
Fülöp G. Á.,
Rutkai I.,
Pásztor E. T.,
Fagyas M.,
Kalász J.,
Édes I.,
Tóth A.,
Papp Z.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12488
Subject(s) - vasoconstriction , chemistry , vasodilation , myeloperoxidase , vasomotor , medicine , endocrinology , cyclooxygenase , vascular smooth muscle , pharmacology , biochemistry , smooth muscle , enzyme , inflammation
Aims Myeloperoxidase ( MPO ) catalyses the formation of a wide variety of oxidants, including hypochlorous acid ( HOC l), and contributes to cardiovascular disease progression. We hypothesized that during its action MPO evokes substantial vasomotor responses. Methods Following exposure to MPO (1.92 mU mL −1 ) in the presence of increasing concentrations of hydrogen peroxide (H 2 O 2 ), changes in arteriolar diameter of isolated gracilis skeletal muscle arterioles ( SMA s) and coronary arterioles ( CA s) and in the isometric force in basilar arteries ( BA s) of the rat were monitored. Results Myeloperoxidase increased vascular tone to different degrees in CA s, SMA s and BA s. The mechanism of increased vasoconstriction was studied in detail in SMA s. MPO ‐evoked vasoconstrictions were prevented by the MPO inhibitor 4‐aminobenzhydrazide (50 μ m ), by endothelium removal in the SMA s. Surprisingly, the HOC l scavenger L‐methionine (100 μ m ), the thromboxane A2 ( TXA 2) antagonist SQ ‐29548 (1 μ m ) or the non‐specific cyclooxygenase ( COX ) antagonist indomethacin (1 μ m ) converted the MPO ‐evoked vasoconstrictions to pronounced vasodilations in SMA s, not seen in the presence of H 2 O 2 . In contrast to noradrenaline‐induced vasoconstrictions, the MPO ‐evoked vasoconstrictions were not accompanied by significant increases in arteriolar [Ca 2+ ] levels in SMA s. Conclusion These data showed that H 2 O 2 ‐derived HOC l to be a potent vasoconstrictor upon MPO application. HOC l activated the COX pathway, causing the synthesis and release of a TXA 2‐like substance to increase the Ca 2+ sensitivity of the contractile apparatus in vascular smooth muscle cells and thereby to augment H 2 O 2 ‐evoked vasoconstrictions. Nevertheless, inhibition of the HOC l– COX – TXA 2 pathway unmasked the effects of additional MPO ‐derived radicals with a marked vasodilatory potential in SMA s.