Page 103 - Cardiac Nursing

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C HAPTER 3 / Regulation of Cardiac Output and Blood Pressure 79
levels of ANP may offset the detrimental effects of increased an- is converted to angiotensin II by an angiotensin-converting en-
giotensin–aldosterone and the sympathetic nervous system. 111,119 zyme (ACE) located in the plasma and vascular endothelium (pri-
Clinically, the short-term administration of intravenous BNP marily pulmonary). 132 Pharmacologically, ACE inhibitors exert
nesitiride (Natrecor) has been shown to improve hemodynamic their effect at this level of the RAAS. 133
function and decrease symptoms of acute decompensated heart Angiotensin II has two receptors (AT1 and AT2). The classic
failure compared with standard therapy 120–122 . However, meta- actions of angiotensin II, which are primarily mediated through
analyses indicate that there may be increased risk of worsening re- AT1, include vasoconstriction and stimulation of aldosterone re-
nal failure and increased 30-day mortality; 123–125 thus caution lease. Angiotensin II causes vasoconstriction of the arterioles
must be taken when administering this medication. 126 through a direct effect on the vascular smooth muscle and indi-
C-type natriuretic peptide, which is stored in endothelial cells, rectly affects vascular tone by stimulating the formation of super-
acts in a paracrine fashion and binds to natriuretic peptide recep- oxide anions, which inhibit nitric oxide-mediated vasodilation,
tor C (NPR-C), which is located in vascular smooth muscle. Note and by inducing endothelin-1 formation to cause further vaso-
that other texts refer to binding to NPR-A. 91 CNP couples to in- constriction. 134–136 Angiotensin receptor blockers work primarily
hibitory G proteins (G i ) and causes inhibition of adenylate cyclase on the AT1 receptors.
and activation of phospholipase-C leading to vasodilation. ANP The renal and splanchnic circulations are particularly sensitive
also binds to NPR-C with similar inhibitory effects. 117 Recent to angiotensin II. Angiotensin II increases vascular resistance and
research suggests that CNP may be an endothelium-dependent stimulates the heart indirectly through its potentiating actions on
hyperpolarizing factor, with actions in the peripheral and coro- the sympathetic nervous system. These effects include: (1) accel-
nary vasculature 117,127–129 (see Chapter 2). The peripheral vascular erating the synthesis and release of norepinephrine; (2) delaying
effect of CNP decreases venous return and subsequently decreases neuronal reuptake of norepinephrine; (3) directly stimulating the
cardiac filling pressures, cardiac output, and arterial blood pres- sympathetic ganglia; and (4) facilitating the response to sympa-
sure. Unlike ANP and BNP, CNP has minimal renal actions. 130 thetic activity and vasoconstrictor drugs. 70
CNP is a potent coronary vasodilator and also has an antimito- Angiotensin II also has a long-term effect on blood pressure
genic effect on vascular smooth muscle, which may be protective through stimulation of aldosterone synthesis and secretion, which
against atheroma development and restenosis. 131 Additionally, in increases blood volume. Aldosterone, a mineralocorticoid synthe-
an experimental model of myocardial infarction, CNP adminis- sized and secreted by the adrenal cortex, increases sodium reab-
tration decreased the size of the infarct and myocardial dysfunc- sorption in the loop of Henle and decreases sodium excretion,
tion and protected against ischemic reperfusion injury, with pos- which together lead to retention of water and expansion of blood
sible mechanisms including CNP/NPR-C related coronary volume. The change in blood volume is a slow process, which is
vasodilation and decreased heart rate. 127 important in the long-term control of blood pressure. Angiotensin
II may also play a role in a sustained increase in sympathetic va-
Renin–Angiotensin–Aldosterone somotor or cardiac sympathetic activity by modification of sym-
System pathetic nervous system activity perhaps by action at the level of
the paraventricular nucleus. 8,37 This latter mechanism may con-
The RAAS plays an important role in the long-term control of ar- tribute to long-term control of sympathetic activity.
terial blood pressure, regional blood flow, and sodium balance. The In 2000 ACE2 was discovered. 137,138 This enzyme hydrolyzes
RAAS acts in a cascade fashion, initiated by the stimulation of angiotensin (Ang) I to produce Ang-(1-9), which is subsequently
renin release from the kidney. Renin is stored in and released from catalyzed by neutral endopeptidase 24.11 (NEP) to produce
the juxtaglomerular cells near the renal afferent arterioles. Renin Ang-(1-7). Angiotensin II can also be converted to Ang-(1-7).
release is stimulated by three mechanisms. First, renin release oc- The receptor for Ang-(1-7) is Mas, which is located in the vascular
curs in response to increased sympathetic nervous system stimula- wall and in myocardial cells. Ang-(1-7) has antiproliferative and
tion of the afferent and efferent arterioles in the renal glomeruli. vasodilator effects, which counterbalance the effects of the
The -adrenergic receptors in the cells of the juxtaglomerular ap- RAAS. 139 The role of Ang-(1-7) and the potential therapeutic
paratus are sensitive to neurally released and systemic cate- benefit of Ang-(1-7) remains under investigation.
cholamines. This neurally mediated response can be blocked by -
adrenergic blockers (e.g., propranolol). Second, renin release is Kallikrein–Kinin System
stimulated by decreased renal perfusion pressure, distending the af-
ferent arterioles (intrarenal baroreceptor pathway). Below a mean The tissue KKS plays a role in blood pressure control and has pro-
arterial pressure of 80 to 90 mm Hg, renin secretion is a steep and tective cardiovascular effects. Kinins (e.g., bradykinin and kallidin
linear function of renal perfusion pressure. Finally, decreased or lys-BK), which are produced by the action of the enzyme hK1
sodium chloride concentration in the macula densa, which is lo- (a kallikrein) on kininogens, bind with B 1 and B 2 receptors.
cated in the early distal tubule, stimulates the juxtaglomerular ap- Bradykinin is inactivated rapidly ( 15 seconds) by ACE. Binding
paratus to secrete renin. Increased blood pressure decreases renin of kinins with the inducible B 1 -receptor, which is up-regulated
release by activating the baroreceptors causing a decrease in sym- during inflammation and tissue injury, causes the release of nitric
pathetic tone, increasing pressure in the renal arterioles, and de- oxide and prostacyclin (PGI 2 ) from endothelial cells and subse-
creasing sodium chloride reabsorption in the proximal tubule, quent vasodilation. The constitutive B 2 receptors play a role in
causing increased sodium chloride to reach the macula densa. pathological conditions such as pain, inflammation and hyperten-
Angiotensin II is released through the proteolytic effects of sion. Stimulation of the B 2 receptor causes the release of nitric ox-
renin on the plasma protein, angiotensinogen, which is synthe- ide and PGI 2 and may be cardioprotective via vasodilation and
sized and released into the plasma from the liver. Renin converts anti-ischemic and antiproliferative effects. 140,141 Bradykinin plays
angiotensinogen to angiotensin I. Angiotensin I, which is inactive, a role in blood pressure regulation via antagonism of angiotensin-