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Cardiovascular Pharmacology > Control of Vascular Smooth Muscle > Flashcards

Control of Vascular Smooth Muscle Flashcards

1
Q

What are the regulatory mechanisms of vascular smooth muscle?

A

ANS

Endothelium

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2
Q

What are the layers of the endothelium of the vasculature?

A

tunica externa
tunica media
tunica intima

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3
Q

what is the tunica externa?

A

loose connective tissue keeping the vessel together

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4
Q

What is the tunica media?

A

smooth muscle

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5
Q

What is the tunica intima?

A

endothelial cells lining the vasculature

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6
Q

What are the features of arteries?

A

large lumen to facilitate flow
lots of muscle
conduit of blood

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7
Q

What are the features of veins?

A

limited smooth muscle
60% of the blood when body at rest
capacitors

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8
Q

What are the features of arterioles?

A

high resistance

fine regulators of blood perfusion

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9
Q

What are the features of capillaries?

A

no smooth muscle
single layer of epithelium
can’t contract or dilate

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10
Q

What is the approximate BP of capillaries?

A

2mmHg

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11
Q

How is the amount of blood in the capillary bed regulated?

A

the precapillary sphincter muscles and small artery and arteriolar resistance

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12
Q

What maintains unidirectional flow in veins?

A

venous valves

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13
Q

How may drugs influence the blood flow and vessels?

A

antagonising, blocking, inhibiting endogenous proteins or activating the endogenous proteins

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14
Q

Give an example of drugs that may interact with cell surface receptors

A

Angiotensin receptor blockers - Losartan

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15
Q

Give an example of drugs that antagonise nuclear receptors

A

mineralocortocoids receptor antagonist - spironolactone

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16
Q

Give an example of drugs that inhibit enzymes

A

ACE inhibitors - ramipril

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17
Q

Give an example of drugs that inhibit ion channels

A

Na Channel Blockers - lidocaine

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18
Q

Give an example of drugs that inhibit transporters

A

inhibitors of Na-K-2Cl symporter i.e. loop diuretics - furosemide

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19
Q

Give an example of drugs that inhibit signal transduction

A

Type 5 PDE inhibits - sildefanil

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20
Q

Give examples of how drugs might activate endogenous proteins

A

enzyme activators - GTNs activate guanylate cyclase

ion channel openers - K channel opener - minoxidil

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21
Q

what is compliance?

A

rigidity - when a vessel is compliant it is less stiff

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22
Q

what is afterload?

A

the stretch the l.ventricle undergoes to eject blood into the aorta

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23
Q

what is preload?

A

the end diastolic volume that stretches the l.ventricle prior to contraction

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24
Q

How might arterial compliance be affected by drugs?

A

anti-hypertensives - diuretics, ACE inhibitors, b-blockers
hypolipidemic agents - statins
anti-diabetic agents - thiazolidinediones
Treatment of congestive HF - ACE inhibitors, nitrates

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25
What is the pressure wave?
the reflection of pressure back towards the heart at resistance points i.e. when the artery bifurcates
26
what happens to the pressure wave in patients with poor compliance?
it comes back quicker
27
what is the consequence of the faster returning pressure wave?
an increase in afterload -> hypertrophy -> heart attack and HF lower diastole -> poor blood flow to coronary arteries -> ischemia increased systolic pressue -> risk factor for stroke
28
how is contraction and maintenance of vascular tone mediated?
increases in IC Ca
29
Where might calcium be released from?
SR | plasma membrane channels VGCC or ROCC
30
What does calcium bind to influence contraction?
Ca - Calmodulin -> CaCaM + MLCK
31
What is the result of calcium-calmodulin binding MLCK?
phosphorylation of myosin
32
what is the result of myosin phosphorylation?
can bind actin to form actomyosin-P to cause contraction
33
How might increases in IC Ca cause a further increase in IC Ca?
activation of IP3R or RyRs
34
What hormones might act to regulate calcium increases?
AngII, NAdr, ET-1
35
How do calcium sparks act as a positive feedback?
increase smooth muscle contractility
36
How do calcium sparks act as a negative feedback on contractility?
activation of Ca-sensitive K channels to cause hyperpolarisation causing limited constriction
37
What underlies the process of calcium sensitisation?
phosphorylation of MLCP'tase inactivates the enzyme | agonist mediated activation of the rho/rho kinase pathway
38
What underpins the process of vascular relaxation?
inhibition of Ca entry hyperpolarisation of sm muscle membrane increased cytoplasmic cAMP or cGMP inhibition of Rho/Rho Kinase
39
What do Ca Channel antogonists do?
block stimulated Ca influx
40
What are some examples of Calcium channel blockers?
amlopidine, nifidepine
41
What do Ca Channel blockers NOT do?
inhibit IC Ca release by specific agonists reduce passive Ca entry stimulate Ca Extrusion
42
How is the SMC hyperpolarised?
closure of the VGCC activation of Na-K-ATPase Activation of K channels
43
What inhibits the Na-K ATPase?
ouabain
44
What is the ratio of ions transported by the Na-K ATPase?
3 Na out for 2 K in
45
What is the result of opening of K channels?
relaxation and hyperpolarisation
46
What are the features of Kca channels?
present in SMC in most vascular beds produce high amplitude K currents expression is upregulated in pathological conditions i.e. arterial hypertension
47
What are the features of Kv channels?
widely distributed and activated by membrane depolarisation limited response to vasoconstrictors altered expression may lead to pulmonary vasoconstriction and primary pulmonary hypertension
48
What can cause pulmonary vasoconstriction and primary pulmonary hypertension?
altered expression of Kv channels
49
What are the features of Kir channels?
voltage-dependent opening at more neg. potential | greatest expression in resistance arteries
50
What are the features of Katp channels?
regulated by IC ATP | low activity in resting conditions
51
What does cGMP activate?
PKG
52
What does cAMP activate?
PKA
53
How does PKG act?
to increase calcium uptake into SR and inhibit Ca influx
54
How does PKA act?
to remove calcium to SR
55
How do PKA and PKG act to prevent contraction?
dephosphorylate MLC
56
What increases levels of cAMP and cGMP?
inhibitors of PDEs
57
What is the dominant pathway of the ANS?
sympathetic nerves
58
Where are the baroreceptors held?
carotid sinus and aortic arch
59
What do the baroreceptors respond to?
temperature changes outside communications pressure changes
60
What sort of innervation occurs at the sympathetic nerves?
Ach in preganglion -> NA at post ganglionic neuron
61
Where are the ganglia located in the sympathetic NS?
in the spinal cord
62
Where are the ganglia in the parasympathetic NS?
the target organ
63
What are the NTs involved in the parasympathetic NS?
Ach and NO from cholinergic and then nitrergic neurons
64
What does NA activate?
a/b adrenoceptors
65
Where are a1 adrenoceptors located?
large arteries -> increases in Ca
66
Where are a2 adrenoceptors located?
small arteries
67
What is the effect of b-adrenoceptor activation
decreased vasoconstriction
68
What are the types of endothelium?
continuous, discontinuous, fenestrated
69
Which is the most common type of endothelium?
continuous
70
What structures allow the transport of substances between cells?
plasmalemmal vesicles, channels, tight junctions
71
Give examples of endothelium function
``` barrier permeability vascular tone inflammation immunogenic processes homeostasis shear stress sensor vascular growth ```
72
How do bovine aortic endothelial cells adjust to blood flow?
within 6 hours they start to orientate in flow direction and within 24 hours totally orientated to cope with shear stress
73
What is the response of damaged endothelium to Ach?
there is no response
74
What are the endothelium derived vasodilators?
EDRF prostacyclin EDHF
75
What are the endothelium derived vasoconstrictors?
ET-1 | thromboxane
76
What are the three isoforms of NOS?
nNOS - neuronal iNOS - inflammation inducible eNOS - endothelial
77
What are the requirements of NO synthesis?
L-Arginine and O2
78
What are the products of NO synthesis?
NO, L-citruline and NADP
79
What are the common cofactors of NOS isoforms?
FAD, FMN and BH4
80
Why is BH4 so important?
prevents ROS from damaging cells | important for redox uncoupling
81
What inhibits BH4?
oxidative stress
82
What occurs when BH4 is inhibited?
High BP
83
which NOS are produced consituitively?
nNOS and eNOS
84
Where is eNOS located?
membrane bound
85
What is the effect of NO?
vasodilation

Cardiovascular Pharmacology (7 decks)

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