Reactive oxygen species play a key role in vascular disease, pulmonary hypertension, and hypoxic pulmonary vasoconstriction. We investigated contractile responses, intracellular Ca(2+) ([Ca(2+)](i)), Rho-kinase translocation, and phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and of myosin light chain (MLC(20)) in response to LY83583, a generator of superoxide anion, in small intrapulmonary arteries (IPA) of rat. LY83583 caused concentration-dependent constrictions in IPA and greatly enhanced submaximal PGF(2alpha)-mediated preconstriction. In small femoral or mesenteric arteries of rat, LY83583 alone was without effect, but it relaxed a PGF(2)alpha-mediated preconstriction. Constrictions in IPA were inhibited by superoxide dismutase and tempol, but not catalase, and were endothelium and guanylate cyclase independent. Constrictions were also inhibited by the Rho-kinase inhibitor Y27632 and the Src-family kinase inhibitor SU6656. LY83583 did not raise [Ca(2+)](i), but caused a Y27632-sensitive constriction in alpha-toxin-permeabilized IPA. LY83583 triggered translocation of Rho-kinase from the nucleus to the cytosol in pulmonary artery smooth muscle cells and enhanced phosphorylation of MYPT-1 at Thr-855 and of MLC(20) at Ser-19 in IPA. This enhancement was inhibited by superoxide dismutase and abolished by Y27632. Hydrogen peroxide did not activate Rho-kinase. We conclude that in rat small pulmonary artery, superoxide triggers Rho-kinase-mediated Ca(2+) sensitization and vasoconstriction independent of hydrogen peroxide.

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Purpose Osteonecrosis of femoral head remains a major complication of femoral neck fractures. It has been postulated that early internal fixation drastically reduces the incidence of osteonecrosis of the femoral head. However, there is a paucity of literature looking at the effect of time delay to internal fixation on the development of this late complication. In this study, we aim to assess the effect of time delay and method of internal fixation on the development of osteonecrosis in those less than 60 years of age. Methods We retrospectively analysed 92 patients less than 60 years of age who presented with intracapsular neck of femur fractures that underwent internal fixation between 1999 and 2009. ResultsOf the 92 intracapsular fractures, 50 underwent fixation using cannulated screws, 32 using a dynamic hip screw, and ten using a dynamic hip screw with a derotation screw. In total, 13 patients (14.1 %) developed osteonecrosis of the femoral head, the highest incidence being in the cannulated screw fixation group with an osteonecrosis rate of 24 %. We did not find the time delay to internal fixation to be a significant predictor of the development of osteonecrosis. Conclusion Our study demonstrated that the method of internal fixation rather than delay in internal fixation was more predictive of osteonecrosis of the femoral head. We did not find support to the current belief that early surgical fixation of neck of femur fractures reduces the risk of osteonecrosis in patients less than 60 years.