ABSTRACT
Extracellular Ca2+ influx was blocked by L-type Ca2+ channel blocker nifedipine to observe the effects of 15-hydroxyeicosatetraenoic acid on the constriction of rabbit pulmonary artery rings and on the changes of Ca2+ level in the rabbit pulmonary artery smooth muscle cells, and further to investigate the mechanism of the calcium mobilization induced by the 15-HETE under hypoxic conditions. The effect of extracellular Ca2+ on tension of the rabbit PA rings was also studied. Nifedipine (10 µ mol/L) had no effect on 1 µ mol/L 15-hydroxyeicosatetraenoic acid induced vasoconstriction under normoxic and hypoxic conditions. Intracellular Ca2+ increased markedly in the 15-HETE group (cells were exposed to 1 µ mol/L 15-HETE for 8 min during culture) compared to the control group (P < 0.05). The study demonstrated that the 15-HETE could induce the elevation of Ca2+ in the pulmonary artery smooth muscle cells and the elevated calcium came from the release of the intracellular calcium.
ABSTRACT
Hypoxic pulmonary hypertension(HPH) is a common disease featured by acute hypoxic pulmonary vasoconstriction(HPV) and chronic hypoxic pulmonary vascular remolding(HPVR) leading to the sustained increasing of pulmonary artery pressure.There are many mediators involved in the HPH but none can illustrate it successfully.Primary work has found 15-lipoxygenase(15-LO) and its catalyzed production 15-hydroxyeicosatetraenoic acid(15-HETE)(from arachidonic acid) are up-regulated in pulmonary vascular when exprosed to hypoxia.And it has been found 15-LO/15-HETE involved in many processes of both the HPV and HPVR,indicating 15-LO/15-HETE may be an important mediator of HPH.Advances research on 15-LO/15-HETE may illustrate the mechanism of HPH,and will give some message in looking for a potential clinical target of HPH.
ABSTRACT
Objective:To investigate the changes of leukotriene B4(LTB4)、15-hydroxyeicosatetraenoic acid(15-HETE)in lung of an animal model with chronic obstructive pulmonary disease(COPD),and the effects of ipratropium.Methods:Thirty-six male Wistar rats were randomized into three groups,Group A(normal controls,group B(COPD),group C(smoking+ipratropium),with 12 rats in each group.Group C receiving inhaling ipratropium 0.025%10ml and once a day for 23 days.Pulmonary functions of the rats were assessed, concen-trations of LTB4 15-HETE in lung tissue were measured by RP-HPLC.Results:The lung functions of FEV0.3/FVC%in COPD rats declined obviously(P0.05). Conclusion:Our results suggest that LTB4 and 15-HETE are involved in airway inflammation in COPD.Ipratropium is effective in decreasing the levels of LTB4 and 15-HETE in lung tissue of COPD rats,and attenuating inflammatory changes of airways.