Vascular

Question 1

what is vascular contraction induced by

Answer 1

increased cytosolic Ca via 2 parallel pathways

Question 2

what are the pathways to increase cytosolic [Ca]

Answer 2

1. agonist induced, Gαq/11 - IP3 mediated Ca2+ release from SR
2. Depolarisation-activated Ca2+ influx via L-type VGCaC

Question 3

contraction all depends on…

Answer 3

phosphorylation of the MYOSIN LIGHT CHAIN (MLC)

Question 4

phosphorylated MLC =

Answer 4

contraction

Question 5

if you want to enhance contraction but have a constant level of Ca, you can…

Answer 5

inhibit myosin light chain phosphatase

Question 6

inhibiting MLCP is called

Answer 6

calcium sensitisation

Question 7

inhibiting MLCP can be done in 2 ways:

Answer 7

1. DAG/PKC phosphorylation of CPI-17 (this works through Gαq/11)
2. RhoA pathway, activating ROCK2 (works through Gα12/13)

Question 8

to revers the muscle contraction, and ultimately get relaxation

Answer 8

1. statins
2. PKC inhibitors
3. ROCK inhibitors

Question 9

in order to get relaxation, the cytosolic Ca conc must

Answer 9

decrease

Question 10

reducing amount of cytosolic Ca can be done by

Answer 10

1. reduced calcium influx via L-type VACCs
2. Reuptake by SERCA2a into the SR
3. Extrusion via Ca2+ - ATPase

Question 11

what should be inhibited for relaxation to occur

Answer 11

MLCK (this is phosphorylation-dependant)

Question 12

what should be activated for relaxation to occur

Answer 12

MLCP

Question 13

what can directly inhibit MLCK

Answer 13

cGMP

Question 14

what is the difference between cardiac and vascular?

Answer 14

in vascular, SERCA2a is NOT regulated by phospholamban and Na/Ca exchanger plays little role in the Ca extrusion

Question 15

when ADMA is present, is there vasodilation?

Answer 15

no because ADMA is a competitive inhibitor of NOS

Question 16

ADMA levels are higher in patients with…

Answer 16

hypertension, atherosclerosis, CHF and chronic renal failure

Question 17

name 2 endothelium-derived vasodilators

Answer 17

NO and prostoglandins

Question 18

name a method of vasodilation

Answer 18

endothelium-derived-hyperpolarisation (EDH)

Question 19

3 main groups of drugs to treat systemic hypertension

Answer 19

CCB, receptor antagonists, K channel activators

Question 20

3 main groups of drugs to treat angina

Answer 20

nitrates, CCBs and K channel activators

Question 21

4 main groups of drugs to treat heart failure

Answer 21

CCBs, K channel activators, receptor antagonists and PDE inhibitors

Question 22

4 main groups of drugs to treat pulmonary hypertension

Answer 22

CCBs, PG agonist, endothelin receptor antagonist and PDE inhibitors