南京医科大学《大学英语》Reading Materials (1) for Doctoral Students.docVIP

PAGE PAGE 1 Glamour of Grammar in EMP Dilation of blood vessels can be regulated by a group of labile humoral substances released from the endothelium, namely endothelium-derived relaxing factors (EDRFs). The paradigm-shaking discovery of nitric oxide (NO) as an EDRF decades ago marked the beginning of a new era in cardiovascular research. Upon activation by different stimuli, such as acetylcholine and bradykinin, endothelial cells have their intracellular calcium level increased, which subsequently activates the endothelial NO synthase (eNOS). This leads to the production of NO and citrulline from the substrates L-arginine and molecular O2. NO is released from endothelial cells and stimulates guanylyl cyclase in vascular smooth muscle cells (SMCs). Consequently, cGMP levels in vascular SMCs are elevated and the cells relax (Figure 1). The initial excitement of NO discovery has transformed into many new explorations and triggered wave after wave of aftershocks. It is generally agreed upon that there are more than one EDRF, which are produced by the endothelium and cause blood vessel dilation. Prostacyclin (PGI2) is produced from the endothelium through cyclooxygenase-1, and binds to specific receptors in SMCs and activates adenylate cyclase. Thus, increased cAMP levels in SMCs relax the cells (Figure 1). In most cases, NO-mediated endothelium-dependent vasorelaxation occurs in large conduit arteries whereas the endothelium-dependent relaxation of peripheral resistance arteries does not depend on NO production. After eliminating the endothelial production of NO and PGI2 by knocking out the expression of eNOS and cyclooxygenase-1, there is still residual endothelium-dependent relaxation. Even considering only non-prostanoid EDRF, NO may not be alone. The longstanding mystery surrounding the endothelium-derived hyperpolarizing factor (EDHF) has not been solved, and the roles of other gasotransmitters in endothelium-dependent vasorelaxation have been