1. Regulation of Flow and Pressure

2. Regulation of blood flow in arteries
- Intrinsic control
- Extrinsic control
-- Neural control
-- Hormonal control *

3. Regulation of blood flow in arteries
- Intrinsic control
- Extrinsic control
-- Neural control
-- Hormonal control

4. Autoregulation: Local Regulation of Blood Flow
Autoregulation – automatic adjustment of blood flow to each tissue in proportion to its requirements at any given point in time
Blood flow through an individual organ is intrinsically controlled by modifying the diameter of local arterioles feeding its capillaries
MAP remains constant, while local demands regulate the amount of blood delivered to various areas according to need

5. Regulation of blood flow in arteries
It is important to adjust blood flow to organ needs  Flow of blood to particular organ can be regulated by varying resistance to flow (or blood vessel diameter)
Vasoconstriction of blood vessel smooth muscle is controlled both by the ANS and at the local level.
Four factors control arterial flow at the organ level:
- change in metabolic activity
- changes in blood flow
- stretch of arterial smooth muscle
- local chemical messengers

6. Change in metabolic activity
Usually linked to CO2 and O2 levels (↑ CO2  vasodilation ↑ blood flow) intrinsic control
most important local chemical influences on arteriolar smooth muscle are local changes in metabolism within that organ
local metabolic changes can affect the diameter of an arteriole without neural influence
active hyperemia = local arteriolar vasodilation that increases blood flow into an organ
arterioles are found within an organ and can be directly affected by that organ’s metabolic needs
local metabolic factors
decreased/increased oxygen = vasodilation/vasoconstriction
increase carbon dioxide = vasodilation
increased carbonic acid= vasodilation
increased K+ - repeated APs that outpace the Na/K pump’s ability to correct ionic changes = vasodilation
increased osmolarity – concentration of solutes accumulates in actively metabolic cells = vasodilation
prostaglandin release = vasodilation
relative concentration of these factors can determine the state of arteriolar muscle tone

8. Local Physical factors
Metabolic Controls
Declining tissue nutrient and oxygen levels are stimuli for autoregulation
Hemoglobin delivers nitric oxide (NO) as well as oxygen to tissues
Nitric oxide induces vasodilation at the capillaries to help get oxygen to tissue cells
Other autoregulatory substances include: potassium and hydrogen ions, adenosine, lactic acid, histamines, kinins, and prostaglandins
Local Physical factors
application of heat or cold
heat causes localized arteriolar vasodilation
increases blood flow
cold – counteracts histamine-induced swelling by inducing vasoconstriction

9. - decreased blood flow  increased metabolic wastes  vasodilation
Changes in blood flow
- decreased blood flow  increased metabolic wastes  vasodilation
shear stress
blood flowing over the endothelial lining creates friction = shear stress
increase in shear stress can cause increased release of NO – promotes vasodilation
increased blood flow now reduces shear stress
If you cutoff blood flow temporarily, and then re-open it,
the vessels will try to restore the BP constant even if it means excess Blood Flow. (this is common in strokes)
How?
“back-propagation” of vasodilatation all the way to the arteries :
i.  accumulation of vasodilator metabolites is enough to reach back
ii.  increased arteriolar flow  increased shear stress  endothelium relase of EDRF.

11. Stretch of arterial wall = myogenic response
- Stretch of arterial wall due to increased pressure  reflex constriction
myogenic response to stretch
increased MAP drives more blood into the arteriole which pushes out against the vessel wall = passive stretch
leads to vasoconstriction to reduce this blood volume
arteriolar smooth muscle responds to passive stretch by increasing its tone through vasoconstriction
this increased tone acts to resist the passive stretch
done by the release of vasoactive mediators from the EC (e.g. endothelin)
arterial occlusion can block blood flow and reduce this stretch
arterioles will dilate in response=reactive hyperemia

12. Locally secreted chemicals can promote vasoconstriction or most commonly vasodilation
- inflammatory chemicals, (nitric oxide, CO2)
these local chemical changes do not act directly on smooth muscle but act on the endothelial cells
ECs – simple squamous epithelia cells
found lining the inside of the arteriole and capillary
ECs then release chemical factors called vasoactive mediators
e.g. endothelin = vasoconstriction
e.g. nitric oxide = vasodilation by relaxing arteriolar smooth muscle
inhibits entrance of calcium into the smooth muscle which inhibits the opening of the foot proteins on the sarcoplasmic reticulum
ECs have multiple roles

13. Histamine NOT released by metabolic changes
NOT produce by endothelial cells
released upon pathology
released by connective tissue cells within the organ or by circulating white blood cells (mast cells, basophils)
usually released in response to organ damage
causes vasodilation to increase blood flow and speed healing

14. Regulation of blood flow in arteries
- Intrinsic control
- Extrinsic control
-- Neural control
-- Hormonal control

15. Extrinsic Regulation of Blood Flow
Sympathoadrenal
Increase cardiac output
Increase TPR: Alpha-adrenergic stimulation - vasoconstriction of arteries in skin and viscera
Parasympathetic
Parasympathetic innervation limited, less important than sympathetic nervous system in control of TPR.
Parasympathetic endings in arterioles promote vasodilation to the digestive tract, external genitalia, and salivary glands

17. Extrinsic control of arteriolar diameter
includes both neural and hormonal control
sympathetic division innervates arteriolar smooth muscle everywhere except the brain
NO parasympathetic innervation of arteriolar smooth muscle! (exception – clitoris and penis)
sympathetic activity contributes to arteriolar vascular tone
increased sympathetic activity induces vasodilation of arterioles in heart and skeletal muscle– drops arteriolar resistance and changes MAP
main area of the brain to adjust sympathetic output = cardiovascular control center
other brain regions involved – hypothalamus
Hormones: ADH, angiotensin II, epinephrine, norepinephrine

18. Regulation of blood flow in arteries
- Intrinsic control
- Extrinsic control
-- Neural control
-- Hormonal control

19. HORMONAL CONTROL OF ARTERIOLAR DIAMETER:
angiotensin II – converted from angiotensin I by the enzyme ACE (produced in the lungs)
regulates body’s salt balance
causes the release of aldosterone from the adrenal cortex – increased salt reabsorption
powerful vasoconstrictor
vasopressin (ADH) – released from the posterior pituitary in response to changes in water volume
drop in water content, release of vasopressin, decreased urine volume, increased water retention
also construction of peripheral vessels = vasoconstrictor
plays a role in reducing hemorrhage

20. -Epinephrine and Norepinephrine can be released from the adrenal medulla (sympathetic activity) or NE can be released from neurons (sympathetic)
-Ep and NE can cause vasoconstriction or vasodilation!!! depends on receptor and its location
-NE binds to a1-adrenergic receptors on ALL arteriolar smooth muscle to increase vasoconstriction
-Epi binds to b2-adrenergic receptors on arteriolar smooth muscle in heart and muscles to cause vasodilation
-cerebral arterioles do NOT have a1-adrenergic receptors !!!
-influenced entirely by local physical and chemical changes (intrinsic changes)
-during the “flight or fight” response - Epi is more abundant and has more affinity for the b2-adrenergic receptors which are expressed in large amounts on arteriolar smooth muscle in skeletal and cardiac muscle – so overall effect is vasodilation to heart and skeletal muscles

21. Maintaining Blood Pressure
Maintaining blood pressure requires:
Cooperation of the heart, blood vessels, and kidneys
Supervision of the brain

22. Maintaining Blood Pressure
The main factors influencing blood pressure are:
Cardiac output (CO)
Peripheral resistance (PR)
Blood volume
Blood pressure = CO x PR
Blood pressure varies directly with CO, PR, and blood volume

23. Cardiac Output (CO)
Cardiac output is determined by venous return and neural and hormonal controls
Resting heart rate is controlled by the cardioinhibitory center via the vagus nerves
Stroke volume is controlled by venous return (end diastolic volume, or EDV)
Under stress, the cardioacceleratory center increases heart rate and stroke volume
The end systolic volume (ESV) decreases and MAP increases

24. Cardiac Output (CO)

25. Controls of Blood Pressure
Short-term controls:
Are mediated by the nervous system and bloodborne chemicals
Counteract moment-to-moment fluctuations in blood pressure by altering peripheral resistance
Long-term controls regulate blood volume

26. Short-Term Mechanisms: Neural Controls
Neural controls of peripheral resistance:
Alter blood distribution in response to demands
Maintain MAP by altering blood vessel diameter
Neural controls operate via reflex arcs involving:
Baroreceptors
Vasomotor centers and vasomotor fibers
Vascular smooth muscle

27. Short-Term Mechanisms: Vasomotor Center
Vasomotor center – a cluster of sympathetic neurons in the medulla that oversees changes in blood vessel diameter
Maintains blood vessel tone by innervating smooth muscles of blood vessels, especially arterioles
Cardiovascular center – vasomotor center plus the cardiac centers that integrate blood pressure control by altering cardiac output and blood vessel diameter

28. Short-Term Mechanisms: Vasomotor Activity
Sympathetic activity causes:
Vasoconstriction and a rise in BP if increased
BP to decline to basal levels if decreased
Vasomotor activity is modified by:
Baroreceptors (pressure-sensitive), chemoreceptors (O2, CO2, and H+ sensitive), higher brain centers, bloodborne chemicals, and hormones

29. Short-Term Mechanisms: Baroreceptor-Initiated Reflexes
Increased blood pressure stimulates the cardioinhibitory center to:
Increase vessel diameter
Decrease heart rate, cardiac output, peripheral resistance, and blood pressure

30. Short-Term Mechanisms: Baroreceptor-Initiated Reflexes
Declining blood pressure stimulates the cardioacceleratory center to:
Increase cardiac output and peripheral resistance
Low blood pressure also stimulates the vasomotor center to constrict blood vessels

31. Homeostasis: Blood pressure in normal range
Figure 19.8

32. Figure 19.8 Stimulus: Rising blood Imbalance pressure
Homeostasis: Blood pressure in normal range
Imbalance
Figure 19.8

33. Figure 19.8 Baroreceptors in carotid sinuses and aortic arch
stimulated
Arterial
blood pressure
rises above
normal range
Stimulus:
Rising blood
pressure
Imbalance
Homeostasis: Blood pressure in normal range
Imbalance
Figure 19.8

34. Figure 19.8 Impulse traveling along afferent nerves from
baroreceptors:
Stimulate cardio-
inhibitory center
(and inhibit cardio-
acceleratory center)
Baroreceptors
in carotid
sinuses and
aortic arch
stimulated
Inhibit
vasomotor center
Arterial
blood pressure
rises above
normal range
Stimulus:
Rising blood
pressure
Imbalance
Homeostasis: Blood pressure in normal range
Imbalance
Figure 19.8

35. Figure 19.8 Impulse traveling along afferent nerves from
baroreceptors:
Stimulate cardio-
inhibitory center
(and inhibit cardio-
acceleratory center)
Sympathetic
impulses to
heart
( HR and contractility)
Baroreceptors
in carotid
sinuses and
aortic arch
stimulated
Inhibit
vasomotor center
Rate of vasomotor
impulses allows
vasodilation
( vessel diameter)
Arterial
blood pressure
rises above
normal range
Stimulus:
Rising blood
pressure
Imbalance
Homeostasis: Blood pressure in normal range
Imbalance
Figure 19.8

36. Figure 19.8 Impulse traveling along afferent nerves from
baroreceptors:
Stimulate cardio-
inhibitory center
(and inhibit cardio-
acceleratory center)
Sympathetic
impulses to
heart
( HR and contractility)
Baroreceptors
in carotid
sinuses and
aortic arch
stimulated
Inhibit
vasomotor center CO R
Rate of vasomotor
impulses allows
vasodilation
( vessel diameter)
Arterial
blood pressure
rises above
normal range
CO and R
return blood
pressure to
homeostatic
range
Stimulus:
Rising blood
pressure
Homeostasis: Blood pressure in normal range
Figure 19.8

37. Figure 19.8 Imbalance Homeostasis: Blood pressure in normal range
Stimulus:
Declining
blood pressure
Imbalance
Figure 19.8

38. Figure 19.8 Imbalance Homeostasis: Blood pressure in normal range
Stimulus:
Declining
blood pressure
Imbalance
Impulses from
baroreceptors:
Stimulate cardio-
acceleratory center
(and inhibit cardio-
inhibitory center)
Arterial blood pressure
falls below normal range
Baroreceptors in
carotid sinuses
and aortic arch
inhibited
Figure 19.8

39. Figure 19.8 Imbalance Homeostasis: Blood pressure in normal range
Stimulus:
Declining
blood pressure
Imbalance
Impulses from
baroreceptors:
Stimulate cardio-
acceleratory center
(and inhibit cardio-
inhibitory center)
Arterial blood pressure
falls below normal range
Baroreceptors in
carotid sinuses
and aortic arch
inhibited
Stimulate
vasomotor
center
Figure 19.8

40. Figure 19.8 Imbalance Homeostasis: Blood pressure in normal range
Stimulus:
Declining
blood pressure
Imbalance
Impulses from
baroreceptors:
Stimulate cardio-
acceleratory center
(and inhibit cardio-
inhibitory center)
Arterial blood pressure
falls below normal range
Baroreceptors in
carotid sinuses
and aortic arch
inhibited
Sympathetic
impulses to heart
( HR and contractility)
Vasomotor
Fibers
stimulate
vasoconstriction
Stimulate
vasomotor
center
Figure 19.8

41. Figure 19.8 Homeostasis: Blood pressure in normal range Stimulus:
Declining
blood pressure
CO and R
return blood
pressure to
homeostatic
range
Impulses from
baroreceptors:
Stimulate cardio-
acceleratory center
(and inhibit cardio-
inhibitory center)
Arterial blood pressure
falls below normal range
Cardiac
output
(CO)
Baroreceptors in
carotid sinuses
and aortic arch
inhibited
Sympathetic
impulses to heart
( HR and contractility)
Peripheral
resistance (R)
Vasomotor
Fibers
stimulate
vasoconstriction
Stimulate
vasomotor
center
Figure 19.8

42. Figure 19.8 Impulse traveling along afferent nerves from
baroreceptors:
Stimulate cardio-
inhibitory center
(and inhibit cardio-
acceleratory center)
Sympathetic
impulses to
heart
( HR and contractility)
Baroreceptors
in carotid
sinuses and
aortic arch
stimulated
Inhibit
vasomotor center CO R
Rate of vasomotor
impulses allows
vasodilation
( vessel diameter)
Arterial
blood pressure
rises above
normal range
CO and R
return blood
pressure to
Homeostatic
range
Stimulus:
Rising blood
pressure
Imbalance
Homeostasis: Blood pressure in normal range
Stimulus:
Declining
blood pressure
Imbalance
CO and R
return blood
pressure to
homeostatic
range
Impulses from
baroreceptors:
Stimulate cardio-
acceleratory center
(and inhibit cardio-
inhibitory center)
Arterial blood pressure
falls below normal range
Cardiac
output
(CO)
Baroreceptors in
carotid sinuses
and aortic arch
inhibited
Sympathetic
impulses to heart
( HR and contractility)
Peripheral
resistance (R)
Vasomotor
fibers
stimulate
vasoconstriction
Stimulate
vasomotor
center
Figure 19.8

43. Short-Term Mechanisms: Chemical Controls
Blood pressure is regulated by chemoreceptor reflexes sensitive to oxygen and carbon dioxide
Prominent chemoreceptors are the carotid and aortic bodies
Reflexes that regulate BP are integrated in the medulla
Higher brain centers (cortex and hypothalamus) can modify BP via relays to medullary centers

44. Chemicals that Increase Blood Pressure
Adrenal medulla hormones – norepinephrine and epinephrine increase blood pressure
Antidiuretic hormone (ADH) – causes intense vasoconstriction in cases of extremely low BP
Angiotensin II – kidney release of renin generates angiotensin II, which causes vasoconstriction
Endothelium-derived factors – endothelin and prostaglandin- derived growth factor (PDGF) are both vasoconstrictors

45. Chemicals that Decrease Blood Pressure
Atrial natriuretic peptide (ANP) – causes blood volume and pressure to decline
Nitric oxide (NO) – is a brief but potent vasodilator
Inflammatory chemicals – histamine, prostacyclin, and kinins are potent vasodilators
Alcohol – causes BP to drop by inhibiting ADH

46. Long-Term Mechanisms: Renal Regulation
Long-term mechanisms control BP by altering blood volume
Baroreceptors adapt to chronic high or low BP
Increased BP stimulates the kidneys to eliminate water, thus reducing BP
Decreased BP stimulates the kidneys to increase blood volume and BP

47. Kidney Action and Blood Pressure
Kidneys act directly and indirectly to maintain long-term blood pressure
Direct renal mechanism alters blood volume
Indirect renal mechanism involves the renin-angiotensin mechanism

48. Kidney Action and Blood Pressure
Declining BP causes the release of renin, which triggers the release of angiotensin II
Angiotensin II is a potent vasoconstrictor that stimulates aldosterone secretion
Aldosterone enhances renal reabsorption and stimulates ADH release

49. Kidney Action and Blood Pressure