Rho kinase signaling mediates increased basal pulmonary vascular tone in chronically hypoxic rats. Am J Physiol Lung Cell Mol Physiol 287: L665-L672, 2004. First published September 5, 2003 10.1152/ ajplung.00050.2003.-Recent evidence suggests that Rho/Rho kinase signaling plays an important role in the sustained vasoconstriction induced by many agonists and is involved in the pathogenesis of systemic vascular diseases. However, little is known about its role in increased vascular tone in hypoxic pulmonary hypertension (PH). The purpose of this study was to examine whether Rho/Rho kinasemediated Ca 2ϩ sensitization contributed to sustained vasoconstriction and increased vasoreactivity in hypoxic PH in rats. Acute intravenous administration of Y-27632, a Rho kinase inhibitor, nearly normalized the high pulmonary arterial blood pressure and total pulmonary resistance in chronically hypoxic rats. In contrast to nifedipine, Y-27632 also markedly decreased elevated basal vascular tone in hypertensive blood-perfused lungs and isolated pulmonary arteries. Y-27632 and another Rho kinase inhibitor, HA-1077, completely reversed nitro-L-arginine-induced vasoconstriction in physiological salt solution-perfused hypertensive lungs, whereas inhibitors of myosin light chain kinase (ML-9), protein kinase C (GF-109203X), phosphatidylinositol 3-kinase (LY-294002), and tyrosine kinase (tyrphostin A23) caused only partial or no reversal of the vasoconstriction. Vasoconstrictor responses to KCl were augmented in hypertensive physiological salt solution-perfused lungs and pulmonary arteries, and the augmentation was eliminated by Y-27632. These results suggest that Rho/Rho kinase-mediated Ca 2ϩ sensitization plays a central role in mediating sustained vasoconstriction and increased vasoreactivity in hypoxic PH.hypoxic pulmonary hypertension; Y-27632; calcium sensitization; RhoA SUSTAINED ABNORMAL VASOCONSTRICTION is one of the major causes of many cardiovascular diseases, including pulmonary hypertension (PH). ]. This is referred to as Ca 2ϩ sensitization (9, 43). Recent evidence indicates that although Ca 2ϩ /calmodulindependent MLCK-mediated MLC phosphorylation is the key factor for triggering VSMC contraction, Ca 2ϩ sensitization is important for the sustained phase of contraction (9, 43).The small GTPase RhoA, a member of the Rho family of small GTP-binding proteins, and its downstream effector Rho kinase (Rho/Rho kinase signaling) play a major role in the regulation of MLCP activity and, thus, Ca 2ϩ sensitization (9, 30, 43). RhoA is activated by various vasoconstrictors, including thromboxane, endothelin-1 (ET-1), and serotonin, the receptors of which are coupled to G proteins. Thus Rho/Rho kinase-mediated Ca 2ϩ sensitization is thought to be a major component in the sustained vasoconstriction induced by G protein-coupled receptor agonists. Selective Rho kinase inhibitors, such as Y-27632 (45) and fasudil (HA-1077) (2, 41, 45), effectively reverse the sustained vasoconstriction induced by many agonists (3,25,34).The pathogenesi...

Background: To compare morphological gross tumor volumes (GTVs), defined as pre-and postoperative gadolinium enhancement on T 1 -weighted magnetic resonance imaging to biological tumor volumes (BTVs), defined by the uptake of 18 F fluoroethyltyrosine (FET) for the radiotherapy planning of high-grade glioma, using a dedicated positron emission tomography (PET)-CT scanner equipped with three triangulation lasers for patient positioning.

In this series, we found no association between the use of caudal regional anesthesia and fistula formation. Location of the starting urethral meatus, prolonged surgical duration, and subcutaneous epinephrine use were associated with fistula formation. Our findings call into question the routine use of epinephrine in hypospadias repair.

No abstract

No abstract