II . Humoral regulation of cardiovascular system 心血管活动的体液调理心血管活动的体液调理l 1. 肾素血管紧张素醛固酮系统(RAAS)l 2. 肾上腺素和去甲肾上腺素l 3. 血管升压素 l 4. 血管内皮生成的活性物质l 5. 心房钠尿肽l 6. 激肽释放酶激肽系统1. Renin-angiotension-aldosterone system(RAA1. Renin-angiotension-aldosterone system(RAA肾素血管紧张素醛固酮系统肾素血管紧张素醛固酮系统肾素血管紧张素醛固酮系统肾素血管紧张素醛固酮系统(RAAS)(RAAS)交感神交感神经兴奋低血低血压NaNa肾球旁球旁细胞胞分泌分泌肾素素 血管紧血管紧张素原张素原AI渴觉渴觉AIIADH心肌肥大心肌肥大血管增生血管增生全身血全身血管收缩管收缩血容量血容量肾脏水肾脏水钠潴留钠潴留下丘脑下丘脑肾上腺皮质肾上腺皮质醛固酮醛固酮ACE1Angiotonin II 血管紧张素血管紧张素II (AII) angiotensinogen ( 2-globulin) renin (kidney ) angiotensin(decapeptide)converting enzyme (pneumoangiogram) angiotensin(octapeptide) +AT1 receptorangiotensinase A angiotensin (heptapeptide) a. The formation of angiotonin 血管血管紧张紧张素生成素生成过过程程 血管血管紧张紧张素原素原 肝合成肝合成 肾肾素素(肾肾近球近球细细胞分泌胞分泌 血管血管紧张紧张素素 10肽肽 (转转化化酶酶,主要在肺血管主要在肺血管) 血管血管紧张紧张素素 8肽肽 AT1受体受体 血管血管紧张紧张素素酶酶A 血管血管紧张紧张素素III 7肽肽 b. Physiological function of angiotensin 血管血管紧张紧张素素的生理作用的生理作用 The systemic arterioles contracts and the peripheral resistance increases. 全身微全身微动脉收脉收缩，外周阻力，外周阻力。 The veins contracts and the returned blood increases. 静脉收静脉收缩，回心血量，回心血量。 Prejunctional modulation, promote the sympathetic nerve ending to excrete NA. 接头前调制，促进交感神经末梢释放NA。 Action on the specific receptors of CNS , the sympathesis vasoconstrictor tone . 作用于中枢特定受体，交感缩血管紧张。 Stimulate the formation and excretion of aldosterone， the reabsorption of sodium and fluid increases and thus the BP increases too. 刺激醛固酮生成分泌，水钠重吸收，血压。(2) Aldosterone 醛固酮醛固酮Synthesis position : adrenal cortex ZG cell合成部位：肾上腺皮质球状带细胞合成部位：肾上腺皮质球状带细胞critical organ :distal tubule 、collecting duct靶器官：远曲小管、集合管靶器官：远曲小管、集合管Function: to keep Na+ and excrete K+ .作用：保作用：保Na+排排K+作用。作用。 mechanism of action作用机制作用机制 醛固酮醛固酮促进小管上皮细胞促进小管上皮细胞Na+ 泵运转泵运转促进生化氧化提供促进生化氧化提供ATP添加管腔膜对添加管腔膜对Na+ 通透性通透性促促进进Na+的的自自动动重吸收重吸收 (保保Na+) 呵斥小管腔呵斥小管腔内负电位内负电位K+被分泌到被分泌到小管液排小管液排K+)2. Adrenaline(Adr) and noradrenaline (NA) 肾上腺素和去甲肾上腺素肾上腺素和去甲肾上腺素 Synthesis postion: 合成部位合成部位1adrenal medulla 肾上腺髓质肾上腺髓质 Adr： 80%, NE ：20% 肾上腺素：肾上腺素：80，去甲肾上腺素，去甲肾上腺素 ：20 2adrenergic nerve ending 肾上腺素能神经末梢肾上腺素能神经末梢 Secrete NA only. 仅分泌少量的仅分泌少量的NA入血。入血。 肾上腺素肾上腺素 强心药强心药去甲肾上腺素去甲肾上腺素 升压药升压药 3. vasopressin (Antidiuretic hormone ) 血管升压素抗利尿激素血管升压素抗利尿激素 Synthesis position： supraoptic nucleus and paraventricular nucleus. Store in posterior pituitary gland and release to blood stream. 合成部位：在下丘脑的视上核和室旁核合合成部位：在下丘脑的视上核和室旁核合成。成。 在神经垂体后叶储存，释放到血液中发扬在神经垂体后叶储存，释放到血液中发扬作用。作用。 V1 receptor: constriction of blood V1 receptor: constriction of blood vessel increase vessel increase in blood in blood pressure.pressure. 结合合V1V1受体：血管收受体：血管收缩, ,血血压。 V2 receptor: reabsorption of H2O V2 receptor: reabsorption of H2O from collecting from collecting duct duct increases.increases. 结合合V2V2受体：受体：肾集合管集合管对水的重吸收水的重吸收。 Physical function 生理功能 In normal condition , the increase in the level of ADH in plasma firstly induces the effect of antidiuresis,and only when its level increases definitely ,the BP increases. ADH plays an important role in the regulation of the volume of extracellular fluid .Under the condition of water bearing , water depletion and blood loss ,the secretion of ADH increases to keep the normal volume of body fluid and maintain the normal BP. 正常情况下，血浆中正常情况下，血浆中ADH浓度升高时浓度升高时首先出现抗利尿效应，当其血浆浓度明首先出现抗利尿效应，当其血浆浓度明显升高时，才引起血压升高。显升高时，才引起血压升高。ADH对对体内细胞外液量的调理起重要作用。在体内细胞外液量的调理起重要作用。在禁水、失水、失血等情况下，禁水、失水、失血等情况下，ADH释释放添加放添加,保管体内液体量，维持动脉血保管体内液体量，维持动脉血压。压。4. Endothelium-derived vasoactive substances 血管内皮生成的血管活性物质血管内皮生成的血管活性物质 (1) Endothelium-derived relaxing substances 血管内皮生成的舒血管物质血管内皮生成的舒血管物质Prostacyclin 前列环素前列环素PGI2)Endothelium-derived relaxing factor NO 血管内皮舒张因子一氧化氮血管内皮舒张因子一氧化氮NO Endothelium-derived relaxing factor NO 血管内皮舒张因子一氧化氮血管内皮舒张因子一氧化氮NOl lIn 1977 Murad In 1977 Murad l l Find glycerol trinitrate educe its Find glycerol trinitrate educe its endothelium- endothelium- l l relaxing effect through NO. relaxing effect through NO. l lIn 1980 FurchgottIn 1980 Furchgottl l Presume Ach educe its its endothelium- Presume Ach educe its its endothelium- relaxing effect through EDRF. relaxing effect through EDRF. l lIn 1987 MoncadaIn 1987 Moncadal l Certificate the EDRF is in fact NO through Certificate the EDRF is in fact NO through the the l l way of “waterfall-type shower way of “waterfall-type shower . .The finding process of NONONO的发现过程的发现过程l l1977197719771977年年年年 默拉德默拉德默拉德默拉德MuradMuradMuradMurad l l 确确确确认认硝酸甘油硝酸甘油硝酸甘油硝酸甘油类类物物物物质质舒舒舒舒张张血管的作用血管的作用血管的作用血管的作用经过释经过释放放放放NONONONO来来来来实现实现。l l1980198019801980年年年年 佛奇戈特佛奇戈特佛奇戈特佛奇戈特(Furchgott)(Furchgott)(Furchgott)(Furchgott)l l 推推推推测测AchAchAchAch经过经过内皮内皮内皮内皮细细胞胞胞胞释释放的放的放的放的EDRFEDRFEDRFEDRF来来来来实现实现其舒血其舒血其舒血其舒血管效管效管效管效应应。l l1987198719871987年年年年 蒙卡达蒙卡达蒙卡达蒙卡达(Moncada)(Moncada)(Moncada)(Moncada)l l 运用运用运用运用“瀑布式淋浴方法瀑布式淋浴方法瀑布式淋浴方法瀑布式淋浴方法证证明明明明EDRFEDRFEDRFEDRF即是即是即是即是NONONONO。Physical function of NONO的生理作用的生理作用ACNOS血管舒张血管舒张精氨酸精氨酸NONOcGMPcGMPCa2+iCa2+i瓜氨酸瓜氨酸NOS NOS 活性：活性：AchAch，缓激激肽，P P物物质，5 5HT,ATPHT,ATPNOS NOS 活性：活性：NANA，ADHADH，AII AII Endothelin 内皮素内皮素 ET) 21肽肽 Vascular endothelial cell excretes , strong vasoconstrictor. 血管内皮血管内皮细细胞分泌的胞分泌的强强缩缩血管物血管物质质。 Endothelin causes first decrease in BP and followed by long-term of the increase in BP. 内皮素在引内皮素在引发长时发长时期血期血压压先出先出现现血血压压。 (2) Endothelium-derived vasoconstrictor substances 血管内皮生成的缩血管物质5. Atrial natriuretic peptide (ANP) 心房钠尿肽心房钠尿肽(ANP) Synthesis position:atrial muscle cell (28 peptides) Synthesis position:atrial muscle cell (28 peptides) 合成部位：心房肌合成部位：心房肌合成部位：心房肌合成部位：心房肌细细细细胞，胞，胞，胞，2828肽肽肽肽 Target organ: heart, blood vessels, kidney, CNS Target organ: heart, blood vessels, kidney, CNS 靶器官：心靶器官：心靶器官：心靶器官：心脏脏脏脏，血管，血管，血管，血管，肾脏肾脏肾脏肾脏，中枢，中枢，中枢，中枢 The blood volume increases, the atrium wall stretches The blood volume increases, the atrium wall stretches ANP . ANP . 血容量添加，心房壁遭到血容量添加，心房壁遭到血容量添加，心房壁遭到血容量添加，心房壁遭到牵牵牵牵拉拉拉拉ANP ANP 。 Physiological function 生理作用生理作用lHR ,CO l 心率心率，心，心输输出量出量。lThe blood vessel dilates and the peripheral l resistance increases.l 血管舒血管舒张张，外周阻力，外周阻力。 lTo inhibit the activity of RAAS system,the secretion of water and sodium increases.l 抑制抑制RAAS系系统统的活性，的活性，肾肾排水排排水排钠钠。lTo inhibit the secretion of ADH . 抑制血管升抑制血管升压压素的素的释释放。放。l 6. Kallikrein-kinin system 激肽释放酶激肽系统激肽释放酶激肽系统KKS) 组织激肽释放酶组织激肽释放酶低分子激肽原低分子激肽原赖氨酰缓激肽赖氨酰缓激肽缓激肽缓激肽激肽酶激肽酶I激肽酶激肽酶II 失活失活高分子激肽原高分子激肽原血浆激肽释放酶血浆激肽释放酶氨氨基基肽酶 Callidin and kallidin is the most intensive Callidin and kallidin is the most intensive vessel-vessel- relaxing substances. Kinin can relax the VSM relaxing substances. Kinin can relax the VSM and and improve the capillary permeability ,but as to improve the capillary permeability ,but as to otherother SM elicit contraction. SM elicit contraction. 缓激肽和赖氨酰缓激肽血管舒张素是知的最剧烈缓激肽和赖氨酰缓激肽血管舒张素是知的最剧烈的舒血管物质。激肽可使血管平滑肌舒张和毛细血管的舒血管物质。激肽可使血管平滑肌舒张和毛细血管通透性增高，但在其他平滑肌那么引起收缩。通透性增高，但在其他平滑肌那么引起收缩。 III . Local regulation of blood flow 血流量的部分调理血流量的部分调理 1. Active hyperemia 自动充血自动充血 2. Blood flow autoregulation 血流的本身调理血流的本身调理 The local regulation of blood flow is the organs and tissues to regulate its arteriole resistance and the blood flow depending on the factors of the organs and tissues but neural an hormonal mechanism. 血流量的部分调理是指器官或组织的微动脉阻力或血流量的改血流量的部分调理是指器官或组织的微动脉阻力或血流量的改动不取决于神经和激素机制，而是取决于器官和组织本身的调动不取决于神经和激素机制，而是取决于器官和组织本身的调理。理。 1. Active hyperemia 自动充血自动充血 The phenomenon of the increase in the blood flow in most organs and tissues when their metabolism activity strengthen is called active hyperemia.It is caused by the relaxation of arterioles as a result of the activity of organs and tissues strengthen. 大多数器官和组织代谢活动加强时表现为血流量添加，称为自大多数器官和组织代谢活动加强时表现为血流量添加，称为自动充血。自动充血是由于器官或组织活动加强时微动脉舒张的动充血。自动充血是由于器官或组织活动加强时微动脉舒张的结果。结果。 The relaxation of arteriole is the result of the change of the concentration of the chemical reconstituent in extracellular fluid,which includes the decrease in OPP, the increase in the concentration of CO2, H+, adenosine, ATP etc. 自动充血时导致微动脉舒张的要素是微动脉周围的 细胞外液化学成份的改动。这些要素包括氧分压降 低、 CO2浓度、H+浓度、腺苷、ATP等升高。2. Blood flow autoregulation 血流量的本身调理血流量的本身调理 When the organ perfusion pressure changes, the arteriole resistance also change to keep the organ blood flow at a constant level, which is called the autoregulation of the blood flow. 当器官灌注压发生变化时，该器官的微动脉阻力也发生改动，使器官的血流量坚持相对恒定的景象称为血流量的本身调理。 器官：肾脏、心脏、脑 The mechanism of the blood flow autoregulationThe mechanism of the blood flow autoregulation血流量本身调理的机制血流量本身调理的机制血流量本身调理的机制血流量本身调理的机制l代谢性机制代谢性机制 metabolism mechanisml肌源性机制肌源性机制 muscle-derived mechanismmetabolism mechanism代谢性机制代谢性机制BP 器官血流量器官血流量氧分氧分压CO2， H+微动脉舒张微动脉舒张血流量恢复血流量恢复自自动充血：充血：组织活活动加加强代代谢产物增多物增多微血管舒微血管舒张代代谢性机制：血流量缺乏性机制：血流量缺乏代代谢产物物积聚聚 微血管舒微血管舒张muscle-derived mechanism肌源性机制肌源性机制血血血血压压牵张牵张血管血管血管血管平滑肌收平滑肌收平滑肌收平滑肌收缩缩微微微微动动脉阻力脉阻力脉阻力脉阻力 血血血血压压牵张牵张血管血管血管血管平滑肌舒平滑肌舒平滑肌舒平滑肌舒张张微微微微动动脉阻力脉阻力脉阻力脉阻力 血容量血容量恢复恢复能够和平滑肌细胞膜上的牵拉敏感性钙通道有关。能够和平滑肌细胞膜上的牵拉敏感性钙通道有关。IV. Blood volume and long term regulation of blood IV. Blood volume and long term regulation of blood pressurepressure 血量和动脉血压的长期调理血量和动脉血压的长期调理 Neural regulation mainly plays a role in the Neural regulation mainly plays a role in the regulation regulation of BP under the condition of the transient of BP under the condition of the transient fluctuation of BP ,and the blood volume is the major fluctuation of BP ,and the blood volume is the major factor influencing the long term regulation of BP .factor influencing the long term regulation of BP . 神经调理主要是在短时间内血压发生变化的情况下起神经调理主要是在短时间内血压发生变化的情况下起 调理作用。动脉血压长期调理的主要要素是血容量。调理作用。动脉血压长期调理的主要要素是血容量。 Renal-body fluid control system 肾肾-体液控制系统体液控制系统 (RAAS)The long term regulation of blood pressure is carrying The long term regulation of blood pressure is carrying out through the kidney to regulate the extracellular fluid out through the kidney to regulate the extracellular fluid volume, which is called Renal-body fluid control system .volume, which is called Renal-body fluid control system .动脉血脉血压的的长期期调理是理是经过肾脏调理理细胞外液量来胞外液量来实现的。的。这种机制又称种机制又称为肾体液控制系体液控制系统。 血容量血容量血血压肾排水排排水排Na+Na+血血压恢复恢复 血容量血容量血血压肾排水排排水排Na+Na+血血压恢复恢复s sa al lt tEssential hypertension The efficacy of renal-body fluid control system The efficacy of renal-body fluid control system to regulate the BP is determined by the influence of to regulate the BP is determined by the influence of the fluctuation of BP to the excretion of sodium and the fluctuation of BP to the excretion of sodium and water of kidney.water of kidney. 肾体液控制系统调理血压的效能取决于血压的变化对肾排肾体液控制系统调理血压的效能取决于血压的变化对肾排水排钠的影响。水排钠的影响。 From the normal level (100mmHg),the BP increased by From the normal level (100mmHg),the BP increased by 10mmHg, the excretion blood volume of kidney will 10mmHg, the excretion blood volume of kidney will increase by several times.increase by several times. 血压从正常程度血压从正常程度100mmHg100mmHg每升高每升高10mmHg10mmHg，肾排泄量可添加，肾排泄量可添加数倍。数倍。 Influencing factor影响要素影响要素1Vasopressin ADH) 血管升血管升压素素 (抗利尿激素抗利尿激素 循循环血量血量 ADH释放放 肾集合管重吸收集合管重吸收 细胞外液量胞外液量 BP 2RAAS系系统 血管收血管收缩，BP AII 醛固固酮保保钠排排钾水重吸收水重吸收细胞外液胞外液 BP In summarize In summarize，the regulation of BP is an intricate the regulation of BP is an intricate process which relates to many mechanisms.The process which relates to many mechanisms.The neural regulation is quick and short-term which is neural regulation is quick and short-term which is carried out through the regulation of the diameter of carried out through the regulation of the diameter of resistance vessels and cardiac activation.However the resistance vessels and cardiac activation.However the long term regulation of BP is mainly undertaken long term regulation of BP is mainly undertaken through the regulation of kidney to the circulation through the regulation of kidney to the circulation blood volume.blood volume. 总总之，血之，血之，血之，血压压的的的的调调理是一个复理是一个复理是一个复理是一个复杂杂的、多种机制参与的的、多种机制参与的的、多种机制参与的的、多种机制参与的过过程。神程。神程。神程。神经调经调理普通是快速的、短期内的理普通是快速的、短期内的理普通是快速的、短期内的理普通是快速的、短期内的调调理，主理，主理，主理，主要是要是要是要是经过对经过对阻力血管口径及心阻力血管口径及心阻力血管口径及心阻力血管口径及心脏脏活活活活动动的的的的调调理来理来理来理来实现实现的，而的，而的，而的，而长长期期期期调调理那么主要是理那么主要是理那么主要是理那么主要是经过肾对经过肾对循循循循环环血量的血量的血量的血量的调调理理理理实现实现的。的。的。的。