1. Regulation of Cardiovascular Activities
Qiang XIA (夏强), PhD
Department of Physiology
Room C518, Block C, Research Building, School of Medicine
Tel:

2. Lecture Outline
Nervous Regulation
Humoral Regulation
Autoregulation

3. Nervous Regulation

4. Innervation of the heart
Cardiac sympathetic nerve
Cardiac vagus nerve
起源origin
节前纤维preganglionic fiber
外周神经节ganglion
节后纤维postganglionic fiber
支配distribution
递质neurotransmitter

7. Cardiac sympathetic actions
Positive chronotropic effect正性变时作用
Positive dromotropic effect正性变传导作用
Positive inotropic effect正性变力作用

8. Cardiac mechanisms of norepinephrine

9. Mechanisms of norepinephrine —increase Na+ & Ca2+ permeability
If , phase 4 spontaneous depolarization, autorhythmicity 
Ca2+ influx (ICa,L) , phase 0 amplitude & velocity , conductivity 
Ca2+ influx (ICa,L) , Ca2+ release , [Ca2+ ]i , contractility 
(CICR)

10. Asymmetrical innervation of sympathetic nerve

11. Cardiac parasympathetic actions
Negative chronotropic effect负性变时作用
Negative dromotropic effect负性变传导作用
Negative inotropic effect负性变力作用

12. Cardiac mechanisms of acetylcholine

13. Mechanisms of acetylcholine —increase K+ & decrease Ca2+ permeability
K+ outward , |MRP| , phase 4 spontaneous depolarization , autorhythmicity 
Inhibition of Ca2+ channel, phase 0 amplitude & velocity , conductivity 
Ca2+ influx , [Ca2+ ]i , contractility 

14. Cardiac effect of parasympathetic stimulation

15. Vagal Maneuvers Valsalva maneuver
A maneuver in which a person tries to exhale forcibly with a closed glottis (the windpipe) so that no air exits through the mouth or nose as, for example, in strenuous coughing, straining during a bowel movement, or lifting a heavy weight. The Valsalva maneuver impedes the return of venous blood to the heart.
Named for Antonio Maria Valsalva, a renowned Italian anatomist, pathologist, physician, and surgeon ( ) who first described the maneuver.

17. Physiological response in Valsalva maneuver
The normal physiological response consists of 4 phases

18. Physiological response in Valsalva maneuver
The normal physiological response consists of 4 phases
Initial pressure rise: On application of expiratory force, pressure rises inside the chest forcing blood out of the pulmonary circulation into the left atrium. This causes a mild rise in stroke volume.
Reduced venous return and compensation: Return of systemic blood to the heart is impeded by the pressure inside the chest. The output of the heart is reduced and stroke volume falls. This occurs from 5 to about 14 seconds in the illustration. The fall in stroke volume reflexively causes blood vessels to constrict with some rise in pressure (15 to 20 seconds). This compensation can be quite marked with pressure returning to near or even above normal, but the cardiac output and blood flow to the body remains low. During this time the pulse rate increases.
Pressure release: The pressure on the chest is released, allowing the pulmonary vessels and the aorta to re-expand causing a further initial slight fall in stroke volume (20 to 23 seconds) due to decreased left ventricular return and increased aortic volume, respectively. Venous blood can once more enter the chest and the heart, cardiac output begins to increase.
Return of cardiac output: Blood return to the heart is enhanced by the effect of entry of blood which had been dammed back, causing a rapid increase in cardiac output (24 seconds on). The stroke volume usually rises above normal before returning to a normal level. With return of blood pressure, the pulse rate returns towards normal.

20. Interaction of sympathetic and parasympathetic nerves

21. Predominance of autonomic nerves

22. Tonus紧张
Cardiac vagal tone心迷走紧张
Cardiac sympathetic tone心交感紧张

23. Innervation of the blood vessels
Vasoconstrictor nerve缩血管神经
Sympathetic vasoconstrictor nerve交感缩血管神经
Vasodilator nerve舒血管神经
Sympathetic vasodilator nerve交感舒血管神经
Parasympathetic vasodilator nerve副交感舒血管神经
Dorsal root vasodilator nerve脊髓背根舒血管神经

25. Cardiovascular Center
A collection of functionally similar neurons that help to regulate HR, SV, and blood vessel tone

26. Vasomotor center
Located bilaterally mainly in the reticular substance of the medulla and of the lower third of the pons
Vasoconstrictor area
Vasodilator area
Cardioinhibitor area – dorsal nuclei of the vagus nerves and ambiguous nucleus
Sensory area – tractus solitarius

30. Vasomotor center

31. Higher cardiovascular centers
Reticular substance of the pons
Mesencephalon
Diencephalon
Hypothalamus
Cerebral cortex
Cerebellum

32. Baroreceptor Reflexes
Arterial baroreceptors
Carotid sinus receptor
Aortic arch receptor
Afferent nerves (Buffer nerves)
Cardiovascular center: medulla
Efferent nerves: cardiac sympathetic nerve, sympathetic constrictor nerve, vagus nerve
Effector: heart & blood vessels

33. Baroreceptor neurons function as sensors in the homeostatic maintenance of MAP by constantly monitoring pressure in the aortic arch and carotid sinuses.

35. Characteristics of baroreceptors:
Sensitive to stretching of the vessel walls
Proportional firing rate to increased stretching
Responding to pressures ranging from mmHg
Receptors within the aortic arch are less sensitive than the carotid sinus receptors

37. The action potential frequency in baroreceptor neurons is represented here as being directly proportional to MAP.

38. i.e., reduce cardiac output
i.e., MAP is
above
homeostatic
set point
i.e., reduce cardiac output
Baroreceptor neurons deliver MAP information to the
medulla oblongata’s cardiovascular control center (CVCC);
the CVCC determines autonomic output to the heart.

39. Reflex pathway

40. Baroreceptor Reflex Control
Click here to play the
Baroreceptor Reflex Control
of Blood Pressure
Flash Animation

41. Typical carotid sinus reflex

42. Physiological Significance
Maintaining relatively constant arterial pressure, reducing the variation in arterial pressure

43. Other Cardiovascular Reflexes
Click here to play the
Chemoreceptor Reflex Control
of Blood Pressure
Flash Animation

44. Humoral Regulation
Vasoconstrictor agents
Vasodilator agents

45. Renin-angiotensin system

46. Juxtaglomerular cell
Renin

47. Physiological effects of angiotensin II
Constricts resistance vessels
Acts upon the adrenal cortex to release aldosterone
Stimulates the release of vasopressin
Facilitates norepinephrine release from sympathetic nerve endings
Stimulates thirst centers within the brain

48. Epinephrine & Norepinephrine
Sources
Epinephrine----
adrenal medulla
Norepinephrine----
sympathetic nerves

49. Catecholamines
Norepinephrine
Epinephrine

50. Effects Epinephrine Norepinephrine
Receptor a-adrenoceptor
b-adrenoceptor
Heart heart rate (in vitro) － (in vivo)
cardiac output ±
Vessels constriction (skin, visceral)
relaxation (SM, liver) －
total peripheral resistance ±
Blood pressure systolic
diastolic ±
MAP
Clinical application positive inotropic pressor agent
agent

52. A 23-year-old woman presents to your emergency service with an anaphylactic reaction after being stung by several bees. She complains of wheezing and shortness of breath. On examination, the client is in acute distress. BP is 98/56 mmHg, PR 110/min, RR 28/min, and temperature 98.7°F. She is immediately treated with supplemental oxygen. In treating this condition further, what drug is required most urgently? A Theophylline B Glucagon C Cimetidine D Methylprednisolone E Epinephrine

53. Vasopressin (antidiuretic hormone, ADH)

55. Endothelium-derived vasoactive substances
Vasodilator factors
PGI2--prostacyclin
EDRF, NO--endothelium-derived relaxing factor, nitric oxide
EDHF--endothelium-dependent hyperpolarizing factor
Vasoconstrictor factors
Endothelin

56. Atrial natriuretic peptide (ANP)
Produces natriuresis and diuresis
Decreases renin release
Reduces total peripheral resistance via vasodilatation
Decreases heart rate, cardiac output

57. Autoregulation Definition:
Intrinsic ability of an organ to maintain a constant blood flow despite changes in perfusion pressure, independent of any neural or humoral influences

60. Myogenic mechanism
The myogenic mechanism is how arteries and arterioles react to an increase or decrease of blood pressure to keep the blood flow within the blood vessel constant
The smooth muscle of the blood vessels reacts to the stretching of the muscle by opening ion channels, which cause the muscle to depolarize, leading to muscle contraction. This significantly reduces the volume of blood able to pass through the lumen, which reduces blood flow through the blood vessel. Alternatively when the smooth muscle in the blood vessel relaxes, the ion channels close, resulting in vasodilation of the blood vessel; this increases the rate of flow through the lumen.

61. From: http://www. umm. uni-heidelberg
Universität Heidelberg > Fakultäten > Medizinische Fakultät Mannheim > CBTM: Kardiovaskuläre Physiologie >

62. From: AJP - Heart October 2008 vol. 295 no. 4 H1505-H1513

63. Metabolic mechanism
Any intervention that results in an inadequate oxygen (nutrient) supply for the metabolic requirements of the tissues results in the formation of vasodilator substances which increase blood flow to the tissues

64. Metabolic mechanism

65. Metarteriole Precapillary Sphincter Capillary Increased Blood Flow
Lack of oxygen?
Formation of vasodilators?
Combination of both??
Metarteriole
Precapillary Sphincter
Capillary
Relaxation of smooth muscle
Increased Blood Flow

66. Metabolic mechanism Hypoxia Tissue metabolites and ions Adenosine
Potassium ions
Carbon dioxide
Hydrogen ion
Lactic acid
Inorganic phosphate

67. The End.