TRPV4 channels dominant role in the temperature modulation of intrinsic contractility and lymph flow of rat diaphragmatic lymphatics

The lymphatic system drains and propels lymph by extrinsic and intrinsic mechanisms. Intrinsic propulsion depends upon spontaneous rhythmic contractions of lymphatic muscles in the vessel walls, and is critically affected by changes in the surrounding tissue like osmolarity and temperature. Lymphatics of the diaphragm display a steep change in contraction frequency in response to changes in temperature, and this, in turn, affects lymph flow. In the present work we demonstrated, in an ex vivo diaphragmatic tissue rat model, that diaphragmatic lymphatics express transient receptor potential channels of the vanilloid 4 subfamily (TRPV4), and that their blockade by both the non-selective antagonist, Ruthenium Red and by the selective antagonist, HC-067047, abolished the response of lymphatics to temperature changes. Moreover, the selective activation of TRPV4 channels by means of GSK1016790A mirrored the behavior of vessels exposed to increasing temperatures, pointing out the critical role played by these channels in sensing the temperature of the lymphatic vessels environment and thus inducing a change in contraction frequency and lymph flow

Lung parenchyma modifications after mechanical ventilation and fluid load

Mechanical ventilation with or without positive pressure in the airways (PEEP) and with or without mild fluid load can cause some modification on the morphology of the lung matrix in the ventral and dorsal lung regions of supine healthy rats. To evaluate the differences between dorsal and ventral areas of the lungs after different strategies of ventilation we subdivided rats in two sets of animals, one without any intravenous infusion, the other one with intravenous infusion of phosphate buffered saline (PBS) maintained during all the mechanical ventilation. Each set was further subdivided in groups which underwent different ventilation strategies, vary- ing the end-expiratory pressure (0 or 5 mmH2O) and the spontaneous/mechanical breathing. At the morphological analysis no signs of parenchyma injury were collected in all the groups of either sets, although were evident differences in alveolar septa thick- ness: in all the not-infused groups submitted to mechanical ventilation was observed a thinning of the alveolar septa combined with a enlargement of the perivascular fluid cuffs both in ventral and dorsal regions. The infused specimens demonstrate a more congested parenchyma with irregular development of perivascular fluid cuffs around lung microvessels. In all groups, the maintaining of the PEEP during the mechanical ventilation induced significative corner and alveolar septa thinning respect to the controls, more accentuate in the ventral regions. In infused groups, we observed general alveolar septa and corner thickening, with reduction of the differ- ences between dorsal and ventral regions. Mechanical ventilation and fluid load may cause injuries to the lung parenchyma, mainly in the ventral region, injuries that seems to be reduced using a positive pres- sure on the airways, as the PEEP, which seemed to be protective for the extracellular matrix of the lung during the mechanical ventilation. The authors gratefully acknowledge the “Centro Grandi Attrezzature per la Ricer- ca Biomedica” of Insubria University for instruments availability

A step-by-step model of phototransduction cascade shows that Ca2+ regulation of guanylate cyclase accounts only for short-term changes of photoresponse

none2A mathematical model of the vertebrate phototransduction mechanism was designed in a modular fashion, in that increasingly complex behaviors can be turned on and off to evaluate the relative involvement of all elements of the phototransduction cascade. The problem was approached by starting with a minimum model in which the intracellular cGMP concentration ([cGMP]i) was determined by guanylate cyclase (GC), whose activity was assumed not to be regulated by any factor (such as Ca2) and by phosphodiesterase (PDE), whose activity was assumed to be proportional to the light intensity. All dependences were subsequently introduced, i.e. the equations describing PDE activation in detail, the Ca2 regulation of GC and the action of intracellular Ca2 buffers. The simulations and fits show that a high-gain, smooth time- and light-dependent PDE activation, a Ca2-dependent GC, and a Ca2- dependent buffer mechanism are required to account for the flash response kinetics in the dark and on dim backgrounds of light, and the effect of exogenous Ca2 buffers to produce responses characterized by slow and damped oscillations and to enhance the low-frequency noise. However, it was not possible to find any set of parameters able to simultaneously interpolate the waveform of the flash responses (in the dark and on a background of light) and the responses to steps of light. It is therefore concluded that at least one more shut-off mechanism (possibly not Ca-dependent) is necessary to fully account for the phenomenology of the light response in rod photoreceptors.mixedA. MORIONDO; RISPOLI G.A., Moriondo; Rispoli, Giorgi

Tissue biomechanics as a modulator of lymphatic function

The lymphatic network represents a good example of how biological structures maximise their efficiency by exploiting the anatomical and biomechanical properties of their microenvironment. Indeed, the stiffness of the extracellular matrix may directly affect the absorptive and/or propulsive nature of a lymphatic vessel, thus exerting an important modulatory role in lymphatic function

Conformational changes of retinal exchanger probed with flash photolysis of novel Ca-caged compounds

3noneMORIONDO A.; ROGOLINO D; RISPOLI GMoriondo, Andrea; Rogolino, D; Rispoli, G