Soluble epoxide hydrolase deficiency attenuates neointima formation in the femoral cuff model of hyperlipidemic mice.

OBJECTIVE: Epoxyeicosatrienoic acids (EETs) have antiinflammatory effects and are required for normal endothelial function. The soluble epoxide hydrolase (sEH) metabolizes EETs to their less active diols. We hypothesized that knockout and inhibition of sEH prevents neointima formation in hyperlipidemic ApoE(-/-) mice. METHODS AND RESULTS: Inhibition of sEH by 12-(3-adamantan-1-yl-ureido) dodecanoic acid or knockout of the enzyme significantly increased plasma EET levels. sEH activity was detectable in femoral and carotid arteries. sEH knockout or inhibition resulted in a significant reduction of neointima formation in the femoral artery cuff model but not following carotid artery ligation. Although macrophage infiltration occurred abundantly at the site of cuff placement in both sEH(+/+) and sEH(-/-), the expression of proinflammatory genes was significantly reduced in femoral arteries from sEH(-/-) mice. Moreover, an in vivo 5-bromo-2'-deoxyuridine assay revealed that smooth muscle cell proliferation at the site of cuff placement was attenuated in sEH knockout and sEH inhibitor-treated animals. CONCLUSION: These observations suggest that inhibition of sEH prevents vascular remodeling in an inflammatory model but not in a blood flow-dependent model of neointima formation.

Magnetic Resonance Imaging of the Lung as an Alternative for a Pregnant Woman with Pulmonary Tuberculosis.

We report a case of a pregnant 21-year-old woman with pulmonary tuberculosis in which magnetic resonance imaging of the lung was used to assess the extent and characteristics of the pathological changes. Although the lung has been mostly ignored in magnetic resonance imaging for many decades, today technical development enables detailed examinations of the lung. The technique is now entering the clinical arena and its indications are increasing. Magnetic resonance imaging of the lung is not only an alternative method without radiation exposure, it can provide additional information in pulmonary imaging compared to other modalities including computed tomography. We describe a successful application of magnetic resonance imaging of the lung and the imaging appearance of post-primary tuberculosis. This case report indicates that magnetic resonance imaging of the lung can potentially be the first choice imaging technique in pregnant women with suspected pulmonary tuberculosis.

Inhalation of the BK(Ca)-opener NS1619 attenuates right ventricular pressure and improves oxygenation in the rat monocrotaline model of pulmonary hypertension.

BACKGROUND: Right heart failure is a fatal consequence of chronic pulmonary hypertension (PH). The development of PH is characterized by increased proliferation of vascular cells, in particular pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells. In the course of PH, an escalated right ventricular (RV) afterload occurs, which leads to increased perioperative morbidity and mortality. BK(Ca) channels are ubiquitously expressed in vascular smooth muscle cells and their opening induces cell membrane hyperpolarization followed by vasodilation. Moreover, BK activation induces anti-proliferative effects in a multitude of cell types. On this basis, we hypothesized that treatment with the nebulized BK channel opener NS1619 might be a therapy option for pulmonary hypertension and tested this in rats. METHODS: (1) Rats received monocrotaline injection for PH induction. Twenty-four days later, rats were anesthetized and NS1619 or the solvent was administered by inhalation. Systemic hemodynamic parameters, RV hemodynamic parameters, and blood gas analyses were measured before as well as 30 and 120 minutes after inhalation. (2) Rat PASMCs were stimulated with PDGF-BB in the presence and absence of NS1619. AKT, ERK1 and ERK2 activation were investigated by western blot analyses, and relative cell number was determined 48 hours after stimulation. RESULTS: Inhalation of a 12 µM and 100 µM NS1619 solution significantly reduced RV pressure without affecting systemic arterial pressure. Blood gas analyses demonstrated significantly reduced carbon dioxide and improved oxygenation in NS1619-treated animals pointing towards a considerable pulmonary shunt-reducing effect. In PASMC's, NS1619 (100 µM) significantly attenuated PASMC proliferation by a pathway independent of AKT and ERK1/2 activation. CONCLUSION: NS1619 inhalation reduces RV pressure and improves oxygen supply and its application inhibits PASMC proliferation in vitro. Hence, BK opening might be a novel option for the treatment of pulmonary hypertension.