257 research outputs found
Pulmonary vasoconstrictor action of KCNQ potassium channel blockers
No full textKCNQ channels have been widely studied in the nervous system, heart and inner ear, where they have important physiological functions. Recent reports indicate that KCNQ channels may also be expressed in portal vein where they are suggested to influence spontaneous contractile activity. The biophysical properties of K+ currents mediated by KCNQ channels resemble a current underlying the resting K+ conductance and resting potential of pulmonary artery smooth muscle cells. We therefore investigated a possible role of KCNQ channels in regulating the function of pulmonary arteries by determining the ability of the selective KCNQ channel blockers, linopirdine and XE991, to promote pulmonary vasoconstriction. Linopirdine and XE991 both contracted rat and mouse pulmonary arteries but had little effect on mesenteric arteries. In each case the maximum contraction was almost as large as the response to 50 mM K+. Linopirdine had an EC50 of around 1 μM and XE991 was almost 10-fold more potent. Neither removal of the endothelium nor exposure to phentolamine or α,β-methylene ATP, to block α1-adrenoceptors or P2X receptors, respectively, affected the contraction. Contraction was abolished in Ca2+-free solution and in the presence of 1 μM nifedipine or 10 μM levcromakalim
Numerical simulation of Gurney flap on SFYT15thick airfoil
No full textAbstractA two-dimensional steady Reynolds-averaged Navier–Stokes (RANS) equation was solved to investigate the effects of a Gurney flap on SFYT15thick airfoil aerodynamic performance. This airfoil was designed for flight vehicle operating at 20 km altitude with freestream velocity of 25 m/s. The chord length (C) is 5 m and the Reynolds number based on chord length is Re=7.76×105. Gurney flaps with the heights ranging from 0.25%C to 3%C were investigated. The shear stress transport (SST) k-ω turbulence model was used to simulate the flow structure around the airfoil. It is showed that Gurney flap can enhance not only the prestall lift but also lift-to-drag ratio in a certain range of angles of attack. Specially, at cruise angle of attack (α=3°), Gurney flap with 0.5%C height can increase lift-to-drag ratio by 2.7%, and lift coefficient by 12.9%, respectively. Furthermore, the surface pressure distribution, streamlines and trailing-edge flow structure around the airfoil are illustrated, which are helpful to understand the mechanisms of Gurney flap on airfoil aerodynamic performance. Moreover, it is found that the increase of airfoil drag with Gurney flap can be attributed to the increase of pressure drag between the windward and the leeward sides of Gurney flap itself
Multiple P2Y receptors couple to calcium-dependent, chloride channels in smooth muscle cells of the rat pulmonary artery
No full textUridine 5'-triphosphate (UTP) and uridine 5'-diphosphate (UDP) act via P2Y receptors to evoke contraction of rat pulmonary arteries, whilst adenosine 5'-triphosphate (ATP) acts via P2X and P2Y receptors. Pharmacological characterisation of these receptors in intact arteries is complicated by release and extracellular metabolism of nucleotides, so the aim of this study was to characterise the P2Y receptors under conditions that minimise these problems. ATP, UTP and UDP (10-4M) evoked oscillating, inward currents (peak = 13-727 pA) in 71-93% of cells. The first current was usually the largest and in the SPA the response to ATP was significantly greater than those to UTP or UDP (P < 0.05). Subsequent currents tended to decrease in amplitude, with a variable time-course, to a level that was significantly smaller for ATP (P < 0.05), UTP (P < 0.001) and UDP (P < 0.05) in the SPA. The frequency of oscillations was similar for each agonist (mean≈6-11.min-1) and changed little during agonist application. The non-selective P2 receptor antagonist suramin (10-4M) abolished currents evoked by ATP in SPA (n = 4) and LPA (n = 4), but pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (10-4M), also a non-selective P2 antagonist, had no effect (n = 4, 5 respectively). Currents elicited by UTP (n = 37) or UDP (n = 14) were unaffected by either antagonist. Contractions of SPA evoked by ATP were partially inhibited by PPADS (n = 4) and abolished by suramin (n = 5). Both antagonists abolished the contractions in LPA
Multiple sites of oxygen sensing and their contributions to hypoxic pulmonary vasoconstriction
No full textOxygen sensing by the pulmonary vasculature is important for the regulation of vessel tone and the matching of lung perfusion to ventilation. Airways hypoxia is a major stimulus for vasoconstriction, which diverts blood from hypoxic alveoli to better ventilated areas of the lung. Several hypotheses have emerged to explain how pulmonary arteries sense a decrease in oxygen and mediate hypoxic pulmonary vasoconstriction (HPV). They differ mainly in where they place the main site of HPV: in the endothelial or smooth muscle cells of the artery wall. HPV probably results from synergistic actions on both cell types, but it can proceed in the absence of endothelium, suggesting that the primary oxygen sensor is the smooth muscle cell and endothelium-derived agents modulate the muscle response. Several oxygen-sensing targets have been identified in smooth muscle, including potassium channels, Ca2+ stores in the sarcoplasmic reticulum (SR) and the Ca2+ sensitivity of the contractile proteins. The evidence for different oxygen-sensing mechanisms in pulmonary vessels is discussed. © 2002 Elsevier Science B.V. All rights reserved
Going with the flow: Smooth muscle TRPM7 channels and the vascular response to blood flow
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The effects of paeonol on the electrophysiological properties of cardiac ventricular myocytes
No full textPrevious studies have shown that "Mudanpi", a Chinese herbal medicine, has a significant cardioprotective effect against myocardial ischaemia. Based on these findings we hypothesised that paeonol, the main component of Mudanpi, might have an effect on the cellular electrophysiology of cardiac ventricular myocytes. The effects of paeonol on the action potential and ion channels of cardiac ventricular myocytes were studied using the standard whole-cell configuration of the patch-clamp technique. Ventricular myocytes were isolated from the hearts of adult guinea-pig by enzymic dispersion. The myocytes were continuously perfused with various experimental solutions at room temperature and paeonol applied in the perfusate. Action potentials and membrane currents were recorded using both current and voltage clamp modes of the patch-clamp technique. Paeonol, at concentrations 160 mu M and 640 mu M, decreased the action potential upstroke phase, an action associated with the blockade of the voltage-gated, fast sodium channel. The effects of paeonol on both action potential and Na+ current were concentration dependent. Paeonol had a high affinity for inactivated sodium channels. Paeonol also shortened the action potential duration, in a manner not associated with the blockade of the calcium current, or the enhancement of potassium currents. These findings suggest that paeonol, and therefore Mudanpi, may possess antiarrhythmic activity, which may confer its cardioprotective effects. (c) 2006 Elsevier B.V All rights reserved
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