血管平滑筋と狭心症治疗药.pptVIP

血管平滑筋と狭心症治療薬 血管、その構造と機能?病態 細胞内Ca2+濃度 [Ca2+]i と収縮弛緩 狭心症治療薬 * Endothelium Basement membrane Histiocyte Collagen/Matrix Internal elastic membrane External elastic membrane Smooth muscle [Adventitia] Vasa vasorum Sympathetic nerve (vasomotor) Desmosome [Intima] [Media] Structure of the coronary artery Two types of nitric oxide (NO) synthesis in endothelium (left, eNOS) and macrophages (right, iNOS). NO causes vasodilation, and NO free radicals are cytotoxic to microbial and mammalian cells. NOS: NO synthase. (Fig. 3-22, Robbins) 図2-12参照 Vascular smooth muscle relaxation and vasodilation Endothelial stimulation Ca2+ influx eNOS activation Activation stimulus Macrophage Microbe Endothelium Citotoxicity NO NO Virchow’s triad in thrombosis. Endothelial integrity is the single most important factor. Note that injury to endothelial cells can affect local blood flow and/or coagulability; abnormal blood flow (stasis or turbulence), in turn, can cause endothelial injury. The factors may act independently or may combine to cause thrombus formation. (Fig.5-12) 冠動脈攣縮 spasm 血管平滑筋の過剰収縮 冠血管狭窄 冠血流量減少 Force of contraction 90 mM KCl (high K contraction) (10 min) Verapamil 10 -5 M Ca2+ channel blocker 冠動脈平滑筋 脱分極depolarization Voltage-dependent L-type Ca2+ channel open Ca2+ influx Force of contraction Ca2+ channel blocker (10 min) Thromboxan A 2 ( agonist contraction) 血小板 血栓形成 血管収縮 Force of contraction (10 min) Thromboxan A 2 ( agonist contraction) 0-Ca2+ solution Ca2+ influx (-) Force of contraction Ryanodine Empty stored Ca2+ (10 min) Thromboxan A 2 ( agonist contraction) Force of contraction Ryanodine Empty stored Ca2+ (10 min) Thromboxan A 2 ( agonist contraction) Verapamil 0-Ca2+ solution Ca2+ influx (-) ニトログリセリン nitroglycerine H2C O NO2 | HC O NO2 | H2C O NO2 グリセリンと硝酸のエステル （軽い揮発性及び脂溶性） 脂溶性→肝臓で脱ニトロ化を受け無効になる ↓ t1/2=2-8 min 主に舌下で投与される（first pass effectを避けるため） ほかに，点滴静注、テープ剤