Neurotrophin-3, but not nerve growth factor, promotes survival of human intestinal mast cells

Neurotrophins are potent regulators of neuronal cell survival and function. Nerve growth factor (NGF) was shown to reduce apoptosis in cord blood-derived mast cells. Here, we examined the effect of the neurotrophins NGF and neurotrophin (NT)-3 on survival and mediator release of human intestinal mast cells. Mast cells isolated from normal intestinal tissue were cultured in the presence of NGF, NT-3, or stem cell factor (SCF) alone or in the presence of SCF together with each neurotrophin. NGF or NT-3 alone did not promote mast cell survival. In contrast, mast cell recovery was increased twofold when mast cells were cultured with NT-3 in addition to SCF for 14 days compared with control. Mast cell recovery was further increased following a combined addition of NT-3, SCF and IL-4. NT-3 mediated mast cell growth was dependent on the primary receptor for NT-3 TrkC. NGF in combination with SCF or with SCF and IL-4 showed no effect on mast cell survival. Histamine release and histamine content per mast cell remained unchanged, whereas leukotriene C4 release decreased if mast cells were cultured with NGF or NT-3 in addition to SCF. In summary, NT-3 affects mature human mast cells by promoting mast cell survival, whereas NGF does not.     

Effect of urapidil on the performance of ischemic myocardium in anesthetized dogs

Summary Urapidil (URA) is used to treat acute hypertension in patients with coronary artery disease, but the effect of URA on the performance of ischemic myocardium has not yet been investigated. The present study was intended to assess the function of ischemic myocardium following URA administration. In eight anesthetized (piritramide) open-chest dogs systolic contraction (dL) and end-diastolic length (edL) of myocardium supplied by the left descending (LAD) and circumflex (LCA) coronary arteries were measured by sonomicrometry simultaneously with aortic pressure (AoP), left ventricular end-diastolic pressure (LVedP), heart rate (HR), stroke volume (SV), and LAD-flow (QLAD). QLAD was reduced by LAD stenosis to about 50% of control, decreasing dLLAD by 55%. Concomitantly, edLLAD increased by about 9% and LVedP by 22%, whereas AoP decreased by 5%. Then, URA was given i.v. (0.25+0.25+0.50+1.0 mg/kg) in 15-min intervals. Following URA, the performance of the non-ischemic area was not systematically affected, but dLLAD increased by about 50%. This could neither be related to the significant reduction in afterload (AoP: –8%), nor to an increase in preload (LVedP and edLLAD did not change significantly), nor to an improved oxygen supply via the LAD (QLAD even decreased), although an increased collateral flow from the LCA could not be excluded. The increase in systolic shortening correlated very closely to a decrease in heart rate (r=–0.92). It is concluded that the improved function of ischemic myocardium following urapidil resulted from a reduced oxygen demand in consequence to the decrease in heart rate.