Vascular function

Question 1

What controls Blood Vessel Constriction?

Answer 1

• circulating hormones
• local release of neurotransmitters from sympathetic nerve endings
• endothelial cells

-Regulation of calcium concentration

Question 2

how does smooth muscle contract?

Answer 2

-Smc contract when [Ca2+] increases
-Vasoconstrictors and vasodilators increase or decrease [Ca2+]
alter sensitivity of contractile machinery to Calcium

Question 3

what is the process for the initiation of contractiion of smooth muscle cells?

Answer 3

-increase in intracellular calcium concentration Ca2+
-Calcium combines with an acid protein called Calmodulin
-Ca-Cal complex activates Myosin Light Chain
Kinase (MLC Kinase) which phosphorylates the 20
kDA light chain of myosin
-Phosphorylation enables molecular interaction of myosin
with actin
-Phosphorylation is a highly regulated process
-Low level phosphorylation maintains smc tone in some
vessels, in the absence of external stimulation.

Question 4

Where does the calcium come from?

Answer 4

calcium enters the intracellular stores from extracellular space through calcium channels (eg. voltage operated L type calcium channels)

Question 5

How is calcium released?

Answer 5

Released form intracellular stores
-Agonists bind to receptors, coupled to G proteins
stimulates phospholipase C (PLC) activity
-PLC acts on the membrane lipid (phosphatidylinositol 4-5
bisphosphate) to catalyse the formation of Diacyl glycerol
(DG) and inositol triphosphate (IP3).
-DG and IP3 are second messengers.
-IP3 binds to receptors on the SR (sarcoplasmic reticulum) which leads to the release of [Ca2+]

Question 6

what additional factors regulate SMC contraction?

Answer 6

Activation of protein kinase C (PKC)
 Ca2+ and DG activates protein kinase C (PKC)
 PKC phosphorylates specific regulatory target proteins

The contractile response is maintained by a Ca
sensitizing mechanism:
 Inhibition of myosin phosphatase by Rho kinase
 This maintains the contractile state, since the myosin
light chain cannot be dephosphorylated.

Question 7

What causes SMC relaxation and what is needed for it?

Answer 7

SMC relaxation occurs when
-the contractile stimulus is removed
-the contractile mechanism is inhibited
-increase in k
it requires a decrease in Ca or increased MLC phosphotase activity

Question 8

how is a decrease in Ca acheived?

Answer 8

Sequestration of calcium into the SR, through an
ATPase (Ca,Mg-ATPase)
 Removal of calcium through a plasma membrane
bound
 ATPase
 Na+/Ca2+ exchangers
 Inhibition of receptor-operated and voltage operated
Ca channels