Page 77 - Cardiac Nursing

6/3
6/3
0
0
0
0/2
009
1
009
0/2
0/2
2-0
68.
2-0
04
04
68.
xd
xd
q
q
q
3 A
p
3 A
e 5
e 5
p
r
r
ta
p
ta
3
3
5:3
1
5:3
Pa
g
g
g
Pa
Pa
0-c
K34
02_
0-c
LWBK340-c02_
LWB K34 0-c 02_ p p pp042-068.qxd 06/30/2009 15:33 Page 53 Aptara a a
LWB
C HAPTER 2 / Systemic and Pulmonary Circulation and Oxygen Delivery 53
pressure control. Exogenous vasopressin may be beneficial in
refractory vasodilatory shock when there is a relative vasopressin CALCIUM
deficiency (e.g., septic shock, intraoperative hypotension). 122
During cardiopulmonary resuscitation, vasopressin increases coro- The major endpoint of extrinsic neurohormonalfactors andlocal
nary and cerebral blood flow, and is part of the protocol for regulation of vascular tone involves a cascade of messengers that
resuscitation of ventricular fibrillation. 123,124 influence calcium movement in and out of the cell or sarcoplas-
mic reticulum, thus influencing the contractile process. 129 Knowl-
Intracellular Signals for Vasodilation and edge of the role of calcium is important because the modulation
Vasoconstriction of calcium flux is the focus of pharmacologic control of vascular
The two major messengers for vasodilation are the intracellular nu- resistance.
cleotides cAMP and cyclic guanosine monophosphate (cGMP). As with cardiac and skeletal muscle, the changes in intracellu-
The primary messenger for vasoconstriction is IP 3 . lar calcium are responsible for vascular smooth muscle contraction
and relaxation. However, unlike skeletal and cardiac muscle in
Cyclic Guanosine Monophosphate. Nitric oxide, atrial
which calcium reverses the inhibitory effect of troponin on the
natriuretic peptides, and nitrovasodilators (e.g., nitroglycerin
actin–myosin interaction, vascular smooth muscle cross-bridge
and nitroprusside) activate membrane bound or soluble guany-
formation and muscle contraction result from the indirect activa-
late cyclase, which generates cGMP from guanosine triphos-
tion of myosin by calcium. 35,130
phate. The cGMP then activates phosphokinase G, which is
thought to decrease intracellular calcium and subsequently cause
vasorelaxation by (1) increasing the uptake or extrusion of cal- Sources of Calcium
cium by the cytoplasm, (2) inhibiting calcium release from the
The increased intracellular calcium comes from an influx of calcium
sarcoplasmic reticulum, (3) regulating the levels of IP 3 , (4) in-
across the sarcolemma andfrom the sarcoplasmic reticulum. 130 The
hibiting calcium-activated potassium channels, and (5) decreas-
ing contractile protein sensitivity to calcium. 125–127 Phosphoki- calcium influx across the sarcolemma is through voltage-gated ion
channels, which are alteredby the activation of the IP 3 -regulated
nase G also directly inhibits MLCK, thus inhibiting contraction.
channels or ryanodine receptors. These receptors display calcium-
Additionally, cGMP hyperpolarizes the cell, which further de- 129,131
creases intracellular calcium. 43 Nitric oxide also, independent of induced calcium release.
cGMP, increases the uptake of cytosolic calcium into the sar-
coplasmic reticulum. 127 Calcium Signaling
Inositol Triphosphate. In response to vasoconstrictor stim- The increased intracellular calcium binds with calmodulin, a
uli (e.g., norepinephrine, AII, and endothelin), the enzyme PLC small protein found in the cytosol of vascular smooth muscle. The
located in the cell wall splits phosphatidyl inositol into IP 3 and di- calcium–calmodulin complex activates the enzyme MLCK, which
acylglycerol (Fig. 2-13). IP 3 is the primary messenger for vaso- in turn phosphorylates the light protein chains of the myosin
constriction and acts on a special calcium-receptor channel on the head. The phosphorylation activates the myosin (increases the
sarcoplasmic reticulum to release calcium, which as described be- ATPase activity) such that the myosin can interact with actin. The
low leads to contraction. Conversely, cGMP inhibits the accumu- process of phosphorylation is considered the primary mechanism
lation of IP 3 , which leads to a decrease in cytosolic calcium levels of smooth muscle contraction. Conversely, a decrease in the cyto-
and vasorelaxation. 128 plasmic calcium concentration inactivates the MLCK and permits
A-II Ca 2
NE
NO Ado
Opie (2003) AT 1 1
■ Figure 2-13 Protein kinase C (PKC)-linked receptors in vas- ET
Gq
cular smooth muscle. For example, the 1-agonist signalling sys- P P P P
A 2
tem is coupled via a G protein to phospholipase C (PLC), which PLC PLC
breaks down phosphatidylinositol 4,5-biphosphate (PIP2) to 1,2- P P
IP 3
diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP 3 ). DAG IP 3 GC AC
is thought to translocate protein kinase C from cytosol to the membrane-
bound
sarcolemma, thereby activating protein kinase C. signals beyond SR
protein kinase C are not clear. IP 3 releases calcium from the DAG cGMP
t t
activates
sarcoplasmic reticulum to initiate contraction in vascular smooth P P PKC Ca 2
cAMP
muscle. Other vasoconstrictors such as angiotensin II and
endothelin act by the same signal system. (From Opie, L. H. Contractile myosin
[2004]. The heart: Physiology from cell to circulation [4th ed., proteins kinase
p. 206]. Philadelphia: Lippincott Williams & Wilkins.) ? Ca 2
l l
calmodulin i i
Relaxation
Sustained Response
Contraction Relaxation