Section Four Cardiovascular Regulatory Mechanisms

1. Section Four Cardiovascular Regulatory Mechanisms • Nervous Regulation • Humoral Regulation • Local control of blood flow

2. I. Nervous Regulation (I) Innervation of the heart and blood vessels

3. Right side Left side Heart rate Myocardial contractility

4. Right side Left side Heart rate Conductivity

5. NE+ß1R Ach+N1R Stellate ganglion Cervical sympathetic ganglia Heart T1-T5 thoracic spinal cord Cardiac Sympathetic Nerve Cardiac Sympathetic tone

6. Cardiac Sympathetic Nerve NE+β1-R Cardiacmuscle Impulses in the noradrenergic sympathetic nerves to the heart increase the cardiac rate , the force of cardiac contraction and cardiac conducting velocity. Function：Positivechronotropic action Positiveinotropic action Positive dromotropic action Blocker: Propranolol

9. Ach+MR Ach+N1R Heart vagal dorsal nucleus and ambiguus nucleusoblongata Intracardiac ganglion Cardiac Vagal Nerve Muscarinic Receptor Cardiac Vagal tone

10. Cardiac Vagal Nerve Ach +MR Cardiac muscle Impulses in the cholinergic vagus to the heartdecrease the cardiac rate ,the force of cardiac contraction and cardiac conducting velocity. Function：Negative chronotropic action Negativeinotropic action Negative dromotropic action K+ Blocker: Atropin

13. Cardiac peptidergic nerves neuropeptide Y vasoactive intestinal peptide calcitonin gene-related peptide opioid peptide

14. Vasomotor Nerves Fiber Vasoconstrictor Nerve Fibers (Sympathetic Vasoconstrictor Nerve Fibers) Vasodilator Nerve Fibers

15. NE+ß2R Ach+N1R paravertebral ganglia prevertebral ganglia blood vessels T1-L2-3 Thoracic-lumbar spinal cord Vasoconstrictor Nerve Fibers NE+αR*

16. Vasoconstrictor Nerve Fibers αReceptor Vessels contract * NE + β2Receptor vasodilator Distribution density： ①Vessels in skin > skeletal muscle and viscera >heart and brain ②A > V ③Most in arteriole ④Lowest in precapillary sphincter ⑤No in capillary

17. Roles of Vasoconstrictor Fibers Sympathetic Vasoconstrictor tone: 1-3 vices/s at rest. • The blood volume of the organ • The interstitial fluid reabsorption • Venous returns

18. Vasodilator Fibers • Sympathetic vasodilator fibers Ach，Skeletal Muscle Arterioles • Parasympathetic vasodilator fibers Ach，mater, salivary gland, external genitals, etc. • Vasoactive intestinal peptide fiber Sweat glands，etc. • Spinal dorsal rootvasodilator fibers

19. (II) CardiovascularCenters Some neurons in central nervous system that control cardiovascular activity are called cardiovascular centers. Cardiovascular center is a collection of functionally similar neurons that regulates HR，SV and blood vessel tone.

20. 1. Medullary cardiovascular center : The most basic cardiovascular center

21. Basic Areas In Medullary Control of Cardiovascular System Rostral ventrolateral medulla Vasoconstrictor Area (1) the cardiac sympathetic center contractility heart rate conductivity Cardiac Sympathetic Discharge Neurons (+) BP (2) the sympathetic vasoconstrictor center Sympathetic Vasoconstrictor Fibers Discharge Vessels constrict BP Neurons (+)

22. Basic Areas In Medullary Control of Cardiovascular System Vasodilator Area Caudal ventrolateral medulla Sympathetic Vasoconstrictor Fibers Discharge Vessels dilate Neurons (+) BP

23. Afferent Relay Area Nucleus of the tractus solitarius, NTS Medulla hypothalamus NTS receives and integrates afferent impulses and then affects activities of other centers.

24. Cardioinhibitory Area vagal dorsal nucleus and ambiguus nucleus oblongata Also called the cardial vagus center

25. 2. High cardiovascular centers

26. (Ⅲ) Cardiovascular reflexes : The nervous regulatory mechanisms for circulation is the cardiovascular reflex.

27. 1. Baroreceptor reflex The carotid sinus and aortic arch receptors. The baroreceptors are stretch receptors. The adequate stimulus: The baroreceptors are stimulated by distention of the vessel wall in which they are located.

28. The carotid sinus and aortic arch receptors monitor changes of the arterial blood pressure. called arterial baroreceptor. called high pressure receptor. More sensitive to the suddenfluctuant pressure change thanslowpersistentpressure change.

29. 100 mmHg

30. Pathway • carotid sinus baroreceptor (+) → the sinus nerve (+) →the glossopharyngeal nerves (+) →the cardiovascular centers, NTS. • aortic arch baroreceptors (+) →(aortic nerve in rabbit) vagi nerve (+) →the cardiovascular centers, NTS.

31. Vasoconstrictor Area Vasodilator Area Cardioinhibitory Center baroreceptor discharge NTS BP↑ Cardiac vagal tone Cardiac sympathetic tone vasoconstrictor nerves BP ↓ to normal level - - + Heart & Vessel Heart rate decrease Cardiac contractility ↓ Cardiac output decrease Vasodilation Peripheral resistance↓ Called Depressor reflex

33. Vasoconstrictor Area Vasodilator Area Cardioinhibitory Center baroreceptor discharge NTS BP ↓ Cardiac vagal tone Cardiac sympathetic tone vasoconstrictor nerves BP ↑ to normal level + + - Heart & Vessel Heart rate increase Cardiac contractility ↑ Cardiac output increase Vasoconstriction Peripheral resistance ↑

34. The carotid sinus baroreceptors are not stimulated by intrasinus pressure between 0 – 60 mmHg (aortic baroreceptors, 0-30mmHg). Between 60 to 80 mmHg, the carotid sinus baroreceptors respond progressively more and more strongly.

35. The response is the greatest at pressure level near the normal mean arterial blood pressure (100 mmHg). At sinus pressure above 180 mmHg, there is no further increase in response.

36. The response is the greatest at pressure level near the normal mean arterial blood pressure (100 mmHg). Functional Curve Baroreceptor reflex

37. Significance Baroreceptor reflex is a negative feedback mechanism that maintains the mean arterial blood pressure at about 100 mmHg. It is two-ways regulation. Its afferent nerves are called buffer nerves. It can be resetting in hypertension.

38. Baroreceptor reflex It can be resetting in hypertension.

39. 2. The cardiovascular reflex induced by Cardiopulmonary Receptor Located in the atrium, ventricle and the big blood vessels walls of the pulmonary circulation. the receptor in atrium called thevolume receptor; also called low pressure receptor. The afferent nerve is vagus nerves. The adequate stimulus: 1) distention of the cardiovascular walls. 2) chemical substances such as prostaglandin, bradykinin etc.

40. Volume Receptor Discharge Vagus nerve (+) BP↑ NTS Peripheral resistance↓ Heart rate decrease Cardiac output↓ ADH↓ Cardiac sympathetic ↓ cardiac vagus ↑ vasoconstrictor nerves↓ Urine volume ↑, blood volume ↓ Blood pressure ↓, to normal level

41. Significance Cardiopulmonary Receptor reflex is a negative feedback mechanism that maintains a constant the blood volume and body fluid.

42. 3. Chemoreceptors Reflex Chemoreceptors:situated in the carotid body and aortic body. Stimulus:PO2 ↓, PCO2 ↑and hydrogen ion (H+) concentration ↑ in the plasma. Pathway:(1) carotid body(+) →carotid sinus nerve → glossopharyngeal nerve → CNS. (2)Aortic body (+) → vagus → CNS.

43. Chemoreceptors Reflex

45. Hypoxia Hypercapnia Acidosis Apnoea Chemoreflex NTS Vasomotor Area respiration heart respiration↑ Heart rate increase Cardiac output increase peripheral resistance↑ Heart rate decrease Cardiac output decrease Vasoconstriction Blood pressure ↑ Blood pressure ↑

46. Significance Chemoreceptors reflex is a negative feedback mechanism that mainly maintains a constant PO2 , PCO2 and hydrogen ion (H+) concentrationin the plasma. But in hypoxia, asphyxia, arterial hypotension, acidosis, chemoreceptors reflex obviously regulates cardiovascular activity to ensure blood and oxygen supply of the brain and the heart.

47. 4. Brain ischemic response means that reduction in brain blood flow stimulates cardiovascular centers to cause obvious increase invasoconstrictor nerves tone and increases in peripheral resistance and arterial pressure, and increase in brain blood flow, improvement of cerebral blood supply.

48. II. Humoral Regulation • Vasoconstrictors • Angiotensin • Norepinephrine/epinephrine • Vasopressin (antidiuretic hormone，ADH) • Vasodilators • Bradykinin • Histamine • Prostaglandins

49. (I) Renin-Angiotensin-System (RAS) Liver Angiotensinogen Renin Kidney Angiotensin I (Ten peptide) Angiotensin-converting enzyme Lung Angiotensin II Angiotensin enzyme A (Eight peptide) Angiotensin III (Seven peptide)

50. Blood Pressure  Renal Blood Flow Renin  Angiotensins   Aldosterone Arteriolar Vasoconstriction  Na+ & Water Retention  Blood Volume  Blood Pressure Sympathetic nerve excites [Na+] in plasm &tubular fluid