Effects of arachidonic acid metabolites on airway sensors / 生理学报

Arachidonic acid (AA) in the cell membrane produces a variety of metabolites by different enzymatic pathways. These lipid metabolites, along with other mediators, play an important role in the inflammatory processes. Many of them can bind directly to the receptors on the sensory endings and initiate electrical impulses to be transmitted to the central nervous system, causing reflex responses. These bioactive AA metabolites may also alter the lung mechanics (mechanical environment of the sensory ending), and in turn, stimulate sensory afferents. In addition, some metabolites may sensitize the sensory endings and make them more responsive to other mechanical or chemical stimulation. These metabolites may also induce other mediators and modulators to cause physiological effects. Furthermore, some of them may attract inflammatory cells to produce a localized effect. In short, AA metabolites may come from different sources and act through multiple pathways to stimulate airway sensors. This brief review is intended to illustrate the underlying mechanisms and help elucidate the inflammatory process in the airways.

Vasorelaxing effect of idoxifene on human internal mammary arteries / 生理学报

The purpose of this study was to investigate the vasorelaxing effect and mechanism of idoxifene (a new estrogen receptor modulator) on human internal mammary artery (HIMA). HIMA segments were harvested from men during coronary artery bypass grafting surgery. Patients with diabetes mellitus, hypercholesterolemia, hypertension, or smoking habit were excluded. The vasorelaxing effect of idoxifene on artery rings from HIMA with and without endothelium was measured by means of perfusion in vitro. Cumulative dose-response to idoxifene in the range of 0.01-10 micromol/L was observed in the presence and absence of NO synthase inhibitor L-NAME. It was also studied whether the vasodilation effect of idoxifene on HIMA was blocked by methylene blue (MB), an inhibitor of guanylate cyclase (GC). The results obtained from idoxifene were compared with those from 17beta-estradiol (E(2)). It was found that idoxifene caused a concentration-dependent relaxation on HIMA. The dose range was from 0.03 micromol/L (minimal vasodilatory concentration) to 3 mmol/L (maximal vasodilatory concentration). It was also found that the vasorelaxation effect of idoxifene on HIMA was dependent on endothelium. E(2) (0.1-100 micromol/L) also resulted in an endothelium-dependent vasorelaxation, but the vessels were 15-fold less sensitive to E(2) than to idoxifene in their vasorelaxation responses. The EC(50) for E(2) was 4.65+/-0.34 micromol/L, compared with 0.32+/-0.02 micromol/L for idoxifene. The mean maximal vasodilatory value of E(2) was 88.3+/-5.7%, compared with 88.6+/-7.2% for idoxifene. Pretreatment with L-NAME (100micromol/L) abolished idoxifene-induced vasodilation virtually by blocking nitric oxide production. The vasorelaxing effect of idoxifene disappeared in the presence of MB (10 micromol/L). These findings demonstrate that idoxifene results in an endothelium-dependent vasorelaxation of HIMA, like estrogen. The effect of idoxifene is more potent than that of traditional estrogen, and is possibly mediated by NO-GC-cGMP pathway.