cell bio > vascular smooth muscle/dysfunction/hypertension > Flashcards

vascular smooth muscle/dysfunction/hypertension Flashcards

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1
Q

when systolic blood pressure exceeds 120 mmHg and diastolic exceeds 80mmHg

A

hypertension

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2
Q

nearly 50% of americans are _____

A

hypertensive

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3
Q

leading causes of death worldwide

A

cardiovascular diseases

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4
Q

hypertension is a major risk factor for the development of _______ diseases

A

cardiovascular

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5
Q

hypertension can lead to this in the brain

A
  • hemorrhage
  • stroke
  • dementia
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6
Q

hypertension can lead to this in the eyes

A

retinopathy

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7
Q

hypertension can lead to this in the kidneys

A

renal failure

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8
Q

elevated blood pressure becomes a problem when it is _____

A

chronic

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9
Q

two types of hypertension

A
  • primary/essential
  • secondary
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10
Q

the rarer hypertension

A

secondary

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11
Q

high blood pressure caused by an identifiable condition

A

secondary

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12
Q
  • chronic high BP w/ no identifiable cause
  • likely results from many interacting risks
A

primary/essential

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13
Q

function of blood pressure equation

A

BP = CO x SVR

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14
Q

volume of blood pumped by heart per unit of time

A
  • CO
  • cardiac output
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15
Q

resistance to blood flow offered by all the systemic vasculature

A
  • SVR
  • systemic vascular resistance
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16
Q

in ppl w/ hypertension but no other disease, _____ is unchanged but ___ is elevated

A
  1. CO
  2. SVR
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17
Q

in ppl w/ hypertension but no other disease, _____ is enhanced and _____ is reduced

A
  1. vasoconstriction
  2. vasodilation
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18
Q

the regulation of BP/balance btwn CO and SVR depends on interactions btwn ______

A

systems

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19
Q

these regulate systemic BP by influencing peripheral vascular resistance

A

resistance arteries

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20
Q

these control capillary pressure and microvascular fluid exchange

A

resistance arteries

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21
Q

these direct blood flow to tissues and organs based on metabolic demands

A

resistance arteries

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22
Q

______ arteries are the most important to maintaining BP

A

resistance

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23
Q

after large arteries, before capillaries

A

resistance arteries

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24
Q

resistance capillaries exist in a partially contracted state. this generates a ______ vascular tone

A

baseline

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25
endothelial cells in the resistance arteries can release mediators like ____
NO
26
the structural, outer layer of a resistance artery
adventitia
27
the adventitial layer receives ______ from the autonomic nervous system
innervation
28
the intrinsic mechanisms of control for the resistance arteries are subject to _____ mechanisms of control
extrinsic
29
smooth muscle: thick filaments
myosin
30
smooth muscle: thin filaments
actin
31
smooth muscle can _____
contract
32
when smooth muscle contracts, it is called _____. describe wht happens
- "cross bridge cycling" - myosin pulls the actin filaments closer together, which brings the dense bodies together - since dense bodies anchored to plasma membrane, the entire smooth muscle cell shortens
33
for cross bridge cycling, what must occur?
myosin must activate via phosphorylation
34
what initiates cross bridge cycling?
phosphorylation of myosin
35
which part of the myosin is phosphorylated?
LC20
36
the kinase which phosphorylates LC20 on the myosin is dependent on ____
calcium
37
which kinase activates LC20 on myosin?
- MLCK - myosin light chain kinase
38
this calcium-binding protein is tethered to myosin light chain kinase
calmodulin
39
a _____ is needed for the relaxation of smooth muscle
phosphatase
40
what DEphosphorylates LC20 on myosin to allow for relaxation?
- MLCP - myosin light chain phosphatase
41
MLCP dephosphorpylates myosin where there are decreases in ____
calcium
42
what reflects the balance of MLCK and MLCP activity?
contraction
43
the four mechanisms which control vascular smooth muscle contraction
- electromechanical coupling - pharmacomechanical coupling - Ca2+ sensitization - endothelium-dependent relaxation
44
what are the three determinants of membrane potential?
- relative ion concentrations inside/outside of cells - activity of electrogenic pumps tht maintain ion concentration gradients - the permeability of the cell membrane to ions through specific ion channels
45
1. the shift of membrane potential to positive values 2. the shift of membrane potential to negative values
1. depolarization 2. hyperpolarization
46
many potassium channels in vascular smooth muscle carry ________, leading to _____ and ______
- outward currents - hyperpolarization - relaxation
47
many sodium/calcium/cation channels in vascular smooth muscle carry ________, leading to _____ and ______
- inward currents - depolarization - contraction
48
molecules which have the ability to shift membrane potential towards contraction/relaxation are called ____/_____
dilators/constrictors
49
most important source of contractile calcium enters VSMCs through...
voltage-gated Ca2+ channels
50
_____ in VSMC membrane potential can be detrimental (vessels clamp shut/hemorrhage otherwise)
fluctuations
51
intracellular store of calcium (liberated by IP3) is in the...
sarcoplasmic reticulum
52
many contractile agonists can also engage in electromechanical coupling by altering membrane potential, via ____
- DAG - other product of PIP2, along w/ IP3 - it can activate protein kinase C
53
what does DAG activate?
PKC protein kinase C
54
what are the two targets of PKC? what happens?
- voltage-dependent calcium channels: increases calcium influx and thus contractile pool of calcium - voltage-gated potassium channels (but become inhibited when phosphorylated by PKC): membrane potential becomes positive, so we end up with influx of calcium from calcium channel
55
what replenishes calcium stores in the sarcoplasmic reticulum?
SERCA
56
how can calcium be pumped out of the cell?
- PMCA (calcium ATPase) - NCX (sodium/calcium exchanger)
57
calcium sensitization is achieved by the ____of ____
- inhibition - MLCP
58
the regulation of ____ activity is a powerful way to regulate the contractile state of smooth muscle
MLCP
59
MLCP is a ____ protein
heterotrimeric
60
most well known calcium sensitization pathways include ____ and ____
- RhoA - RhoK
61
what can RhoK do to MLCP?
- phosphorylation - thus, inactivate it
62
what activates RhoK?
RhoA
63
what activates RhoA?
- Rho GEF (Rho guanine exchange factors) - these exchange Rho-GDP to Rho-GTP bc RhoA is a small GTPase tht needs GTP to be active
64
vascular smooth muscle can relax in response to _____ released from the endothelium
mediators
65
what mediators r released from the endothelium?
- PG12: prostacyclin - NO: nitric oxide
66
what does NO activate after diffusing across the endothelial/smooth muscle cells?
- GC: guanylate cyclase - GC produces cGMP from GTP - cGMP makes PKG (protein kinase G)
67
what does PGI2/prostacyclin activate?
- GPCR - activates AC, which makes cAMP from ATP - cAMP makes PKA (protein kinase A)
68
common downstream target of PKA and PKG? what happens to the target?
- potassium channels - K+ channels are activated when they get phosphorylated by the protein kinases - this increase potassium efflux = hyperpolarization = relaxation
69
pathways that participate in vasoconstriction tend to be _________ pathways that participate in vasodilation tend to be _________
1. up regulated 2. down regulated
70
hallmark feature of hypertension
upregulation of angiotensin
71
endothelial dysfunction occurs due to ________
prod’n of reactive oxygen species due to persistent oxidative stress
72
what does the prod’n of reactive oxygen species lead to in the endothelium?
- uncoupling of eNOS - this causes the reduced prod’n and reduced bioavailability of NO
73
when _____ is unavailable, vasodilation becomes impaired
NO
74
treatment of hypertension: reducing blood volume (3)
- thiazide diuretics - loop diuretics - mineralocorticoid receptor blockers
75
treatment of hypertension: reduce systemic vascular resistance
- angiotensin converting enzyme inhibitors - angiotensin II receptor blockers - dihydropyridine calcium blockers - director vasodilators
76
treatment of hypertension: reduce cardiac output
- beta adrenergic blocking agents
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