Blood vessel function and the distribution of cardiac output

Question 1

Pressure, flow and resistance

Answer 1

Flow = pressure difference/ resistance

Friction between walls and liquid flow generate resistance

Question 2

Resistance in circulation

Answer 2

Circulation is a combination of resistance in series and parallel
Serial resistance provides fine control of blood flow distribution
Parallel resistance minimises overall resistance- reduces the requirement for the heart to generate pressure

Question 3

How resistance to flow is arranged

Answer 3

Resistance in series (flow through tissues)
Resistance controlled by increasing or decreasing the radius of blood vessels
Resistance in parallel (overall flow in the CNS)
Total resistance is minimised, flow is regulated by altering resistance through tissues

Question 4

Mechanisms for changing vascular diameter

Answer 4

Local control: myogenic response, flow-induce shear stress, metabolic control
Central control: sympathetic nervous system (A1 receptors = contraction, B2 receptors = relaxation), parasympathetic nervous system (ACh on M3 receptors), vasoactive hormones (e.g. angiotensin)

Question 5

Local control: myogenic contraction

Answer 5

Increase in intra-luminal pressure causes contraction

Decrease in intra-luminal pressure causes relaxation

Question 6

Flow-induced shear stress

Answer 6

Increase in flow increases shear stress
Activates eNOS to make NO
NO diffuses into muscle and reduces free intracellular Ca2+
Reduced free intracellular Ca2+ = relaxation
Flow becomes more laminar thereby reducing shear stress

Question 7

Endothelium Derived Hyperpolarising Factor (EDHF)

Answer 7

Endothelium-dependent relaxation still seen when eNOS is blocked
Relaxation is associated with hyperpolarisation of the underlying smooth muscle

Question 8

Metabolic control of vascular diameter

Answer 8

Increase in metabolic rate leads to an increase in oxygen demand, decreasing transient tissues oxygen
Acidosis, hypoxia, adenosine release and an increase in extracellular potassium all cause vasorelaxation
Contraction is active (uses ATP), a lack of oxygen decreases the ability to make ATP so vascular relaxation is due to a lack of ATP

Question 9

Sympathetic nervous output

Answer 9

Sympathetic drive to different tissues can be independently regulated
Sympathetic fibres are tonically active
Overall, reduced activity leads to vasodilation, increased activity leads to an increase in peripheral resistance, decrease in local blood flow and decrease in volume

Question 10

Smooth muscle contraction: A1 adrenoceptor stimulation

Answer 10

Stimulation of alpha adrenoceptors activates Gq
Gq activates phospholipase C
PLC converts PIP2 into IP3 and DAG
IP3 causes release of intracellular Ca stores
Increased free intracellular Ca drives actin/myosin interactions resulting in contraction
Contraction is sustained until stimulus removed
Net effect = vasoconstriction

Question 11

Smooth muscle relaxation: B2 adrenoceptor stimulation

Answer 11

Stimulation of B2 adrenoceptors activates Gs
Gs activates adenylyl cyclase
AC converts ATP into cAMP
Elevated levels of cAMP activate protein kinase G
Targets phosphorylated by protein kinase G
Net effect = vasodilation

Question 12

Parasympathetic mediated vasodilation

Answer 12

Stimulation of muscarinic receptors on endothelium activates Gq
Gq activates phospholipase C increasing IP3 production
IP3 causes release of intracellular Ca2+
eNOS is Ca2+ sensitive and so rate of NO production increased
NO and EDRF cause relaxation of underlying smooth muscle