Constriction of pulmonary artery by peroxide: role of Ca2+ release and PKC

TY - JOUR

T1 - Constriction of pulmonary artery by peroxide: role of Ca2+ release and PKC

AU - Pourmahram, Ghazaleh Esmaeil

AU - Snetkov, Vladimir A.

AU - Shaifta, Yasin

AU - Drndarski, Svetlana

AU - Knock, Greg A.

AU - Aaronson, Philip I.

AU - Ward, Jeremy P. T.

PY - 2008/11/15

Y1 - 2008/11/15

N2 - Reactive oxygen species are implicated in pulmonary hypertension and hypoxic pulmonary vasoconstriction. We examined the effects of low concentrations of peroxide on intrapulmonary arteries (IPA). IPAs from Wistar rats were mounted on a myograph for recording tension and estimating intracellular Ca2+ Using Fura-PE3. Ca2+ sensitization was examined in alpha-toxin-permeabilized IPAs, and phosphorylation of MYPT-1 and MLC20 was assayed by Western Not. Peroxide (30 mu M) induced a vasoconstriction with transient and Sustained Components and equivalent elevations of intracellular Ca2+. The transient constriction was strongly suppressed by indomethacin, the TP-receptor antagonist SQ-29584, and the Rho kinase inhibitor Y-27632, whereas sustained constriction Was unaffected. Neither vasoconstriction nor elevation of intracellular Ca2+ was affected by removal Of extracellular Ca2+, whereas dantrolene suppressed the former and ryanodine abolished the latter. Peroxide-induced constriction of permeabilized IPAs was unaffected by Y-27632 but abolished by PKC inhibitors: these also suppressed constriction in intact IPAs. peroxide caused translocation of PKC alpha. but had no significant effect on MYPT-1 or MLC20 phosphorylation. We conclude that in IPAs peroxide causes transient release of vasoconstrictor prostanoids, but Sustained constriction is associated with release of Ca2+ from ryanodine-sensitive stores and a PKC-dependent but Rho kinase- and MLC20-independent constrictor mechanism. (C) 2008 Elsevier Inc. All rights reserved.

AB - Reactive oxygen species are implicated in pulmonary hypertension and hypoxic pulmonary vasoconstriction. We examined the effects of low concentrations of peroxide on intrapulmonary arteries (IPA). IPAs from Wistar rats were mounted on a myograph for recording tension and estimating intracellular Ca2+ Using Fura-PE3. Ca2+ sensitization was examined in alpha-toxin-permeabilized IPAs, and phosphorylation of MYPT-1 and MLC20 was assayed by Western Not. Peroxide (30 mu M) induced a vasoconstriction with transient and Sustained Components and equivalent elevations of intracellular Ca2+. The transient constriction was strongly suppressed by indomethacin, the TP-receptor antagonist SQ-29584, and the Rho kinase inhibitor Y-27632, whereas sustained constriction Was unaffected. Neither vasoconstriction nor elevation of intracellular Ca2+ was affected by removal Of extracellular Ca2+, whereas dantrolene suppressed the former and ryanodine abolished the latter. Peroxide-induced constriction of permeabilized IPAs was unaffected by Y-27632 but abolished by PKC inhibitors: these also suppressed constriction in intact IPAs. peroxide caused translocation of PKC alpha. but had no significant effect on MYPT-1 or MLC20 phosphorylation. We conclude that in IPAs peroxide causes transient release of vasoconstrictor prostanoids, but Sustained constriction is associated with release of Ca2+ from ryanodine-sensitive stores and a PKC-dependent but Rho kinase- and MLC20-independent constrictor mechanism. (C) 2008 Elsevier Inc. All rights reserved.

U2 - 10.1016/j.freeradbiomed.2008.08.020

DO - 10.1016/j.freeradbiomed.2008.08.020

M3 - Article

VL - 45

SP - 1468

EP - 1476

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

IS - 10

ER -