16 research outputs found
Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery
Aims: We investigated the role of src family kinases (srcFK) in agonist-mediated Ca2+-sensitization in pulmonary artery and whether this involves interaction with the rho/rho-kinase pathway.
Methods and results: Intra-pulmonary arteries (IPAs) and cultured pulmonary artery smooth muscle cells (PASMC) were obtained from rat. Expression of srcFK was determined at the mRNA and protein levels. Ca2+-sensitization was induced by prostaglandin F(2 alpha) (PGF(2 alpha)) in alpha-toxin-permeabilized IPAs. Phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and of myosin light-chain-20 (MLC20) and translocation of rho-kinase in response to PGF(2 alpha) were also determined. Nine srcFK were expressed at the mRNA level, including src, fyn, and yes, and PGF(2 alpha) enhanced phosphorylation of three srcFK proteins at tyr-416. In alpha-toxin-permeabilized IPAs, PGF(2 alpha) enhanced the Ca2+-induced contraction (pCa 6.9) approximately three-fold. This enhancement was inhibited by the srcFK blockers SU6656 and PP2 and by the rho-kinase inhibitor Y27632. Y27632, but not SU6656 or PP2, also inhibited the underlying pCa 6.9 contraction. PGF(2 alpha) enhanced phosphorylation of MYPT-1 at thr-697 and thr-855 and of MLC20 at ser-19. This enhancement, but not the underlying basal phosphorylation, was inhibited by SU6656. Y27632 suppressed both basal and PGF(2 alpha)-mediated phosphorylation. The effects of SU6656 and Y27632, on both contraction and MYPT-1 and MLC20 phosphorylation, were not additive. PGF(2 alpha) triggered translocation of rho-kinase in PASMC, and this was inhibited by SU6656.
Conclusions: srcFK are activated by PGF(2 alpha) in the rat pulmonary artery and may contribute to Ca2+-sensitization and contraction via rho-kinase translocation and phosphorylation of MYPT-1
Constriction of Pulmonary Artery by Peroxide: Role of Ca2+ Release and PKC
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 MLC(20) was assayed by Western blot. Peroxide (30 microM) 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 PKCalpha, but had no significant effect on MYPT-1 or MLC(20) 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 MLC(20)-independent constrictor mechanism
Endothelial function in myometrial resistance arteries of normal pregnant women perfused with syncytiotrophoblast microvillous membranes
Microvascular vasodilator response to acetylcholine is increased in women with pre-eclampsia
Effects of Blocked Versus Random Practice on Speech Motor Skill Acquisition and Retention
Impaired vascular function in women with pre-eclampsia observed with orthogonal polarisation spectral imaging
Distortion of maternal-fetal angiotensin II type 1 receptor allele transmission in pre-eclampsia.
Low-Frequency Type-II Radio Detections and Coronagraph Data Employed to Describe and Forecast the Propagation of 71 CMEs/Shocks
The vulnerability of technology on which present society relies demands that
a solar event, its time of arrival at Earth, and its degree of geoeffectiveness
be promptly forecasted. Motivated by improving predictions of arrival times at
Earth of shocks driven by coronal mass ejections (CMEs), we have analyzed 71
Earth-directed events in different stages of their propagation. The study is
primarily based on approximated locations of interplanetary (IP) shocks derived
from type II radio emissions detected by the Wind/WAVES experiment during
1997-2007. Distance-time diagrams resulting from the combination of white-light
corona, IP type II radio, and in situ data lead to the formulation of
descriptive profiles of each CME's journey toward Earth. Furthermore, two
different methods to track and predict the location of CME-driven IP shocks are
presented. The linear method, solely based on Wind/WAVES data, arises after key
modifications to a pre-existing technique that linearly projects the drifting
low-frequency type II emissions to 1 AU. This upgraded method improves
forecasts of shock arrival time by almost 50%. The second predictive method is
proposed on the basis of information derived from the descriptive profiles, and
relies on a single CME height-time point and on low-frequency type II radio
emissions to obtain an approximate value of the shock arrival time at Earth. In
addition, we discuss results on CME-radio emission associations,
characteristics of IP propagation, and the relative success of the forecasting
methods.Comment: Solar Physics; Accepted for publication 2015-Apr-2