Coronary Veins

The coronary venous drainage (see Figure 17-9, B) follows a path generally parallel to the path of the coronary arteries. The cardiac veins converge to empty into a large venous cavity within the right atrium, the coronary sinus. In addition, the thebesian veins (not shown) empty directly into all heart chambers; this venous drainage into the left heart contributes to the normal anatomical shunt that prevents arterial blood from being fully saturated with oxygen. About 75% of coronary venous flow is through the coronary sinus.²

Oxygen Requirements and Coronary Blood Flow

Even at rest, the myocardium extracts about 70% of the oxygen from its arterial blood flow compared with a 25% extraction rate for the whole body.² During exercise, this extraction rate is higher still. Because heart muscle cannot extract much additional oxygen from the blood, the only way it can receive more oxygen is through increased coronary blood flow. Myocardial oxygenation is highly dependent on blood flow.

Myocardial oxygen need is the major factor governing coronary blood flow. Increased metabolic activity and myocardial hypoxia cause the release of a potent coronary vasodilator called adenosine.³

Diastolic Time and Coronary Blood Flow

At rest, coronary blood flow is about 225 mL per minute, or between 4% and 5% of the cardiac output; during heavy exercise, coronary blood flow can triple or quadruple to meet the extra oxygen demands of the myocardium.² Most coronary perfusion occurs during ventricular relaxation (diastole), opposite to flow through other vascular beds of the body. The powerful contractile force of the ventricles during systole compresses the coronary vessels, momentarily stopping or reversing the direction of their blood flow.³ Thus, sufficient diastolic time (normally about two times as long as systolic time) is important for adequate coronary blood flow. Extreme tachycardia, especially in persons with narrowed coronary arteries, may shorten diastolic time so much that coronary blood flow becomes inadequate. In healthy people, the effect of this shortened diastolic time is overridden by the coronary vasodilation that occurs with increased myocardial oxygen demand.

Excitation-Contraction Coupling

Figure 17-15 shows the microanatomy of the thin actin and thick myosin filaments. Thin filaments are composed of two beadlike actin strands twisted in a helical fashion around a “backbone” of stringlike tropomyosin molecules (see Figure 17-15). In the relaxed state, these “strings” of tropomyosin are situated in such a way that they block specialized binding sites on the actin molecules to which myosin filaments are attracted (Figure 17-16, A [top]).⁴ At regular intervals along the twisted actin-tropomyosin structure are troponin molecules, a complex of three protein subunits tightly bound together: troponin I (TnI), troponin T (TnT), and troponin C (TnC) (Figure 17-16, A [top] and B). TnC binds calcium ions, TnI binds to actin, and TnT binds to tropomyosin; the entire troponin complex is attached to the actin filament. The TnI subunit is responsible for inhibiting actin-myosin interaction when the myocardial fiber is in the relaxed state (see Figure 17-16, B); that is, TnI interacts with TnT to hold the tropomyosin molecule in a position that blocks the binding sites of the actin molecule.⁴

The thick myosin filaments (see Figure 17-15, B) consist of numerous individual myosin molecules shaped like golf clubs. Their “shafts” form the length of the myosin bundle with clublike “heads” sticking outward, attracted to the covered binding sites of adjacent actin molecules. The myosin heads are known as cross-bridges

Contraction occurs when a nerve impulse causes acetylcholine to stimulate the muscle cell sarcolemma. The impulse travels deep into the T-tubules causing the sarcoplasmic reticulum to release Ca⁺⁺ ions, which bind with and activate TnC. Activated TnC initiates a complex interaction among all three troponin subunits that removes the inhibitory effect of TnI; this repositions the tropomyosin molecule to expose the binding sites of the actin molecule (see Figure 17-16, A [bottom] and C).

Figure 17-17 illustrates the sequence of events that occur in actin and myosin filament cross-bridge formation; at the top of the figure, the myosin head is still attached to binding sites on the actin filament from the previous cross-bridge cycle. In (1), ATP binds with the myosin head, which reduces its affinity for actin and causes it to detach. In (2), ATP is broken down (hydrolyzed) into adenosine diphosphate (ADP) and inorganic phosphate (P) on the myosin head, causing it to swivel on its hinge so that it is positioned immediately across from a new

binding site farther along on the actin filament. In (3), the myosin head binds to its new position on the actin filament, forming a cross-bridge. This action causes the inorganic phosphate molecule to dissociate from ADP, which causes the myosin head (still attached to the actin filament) to flex on its hinge, pulling the actin filament toward the myosin filament’s tail (the “power stroke”). This action causes ADP to dissociate from the myosin head (5), leaving the actin-myosin complex in a rigid state (top figure). In the absence of ATP, the strong binding state between myosin and actin persists, which would potentially prevent the contractile proteins from relaxing (this occurs soon after death because ATP cannot be generated, creating a state known as rigor mortis). In living muscle cells, metabolism generates new ATP molecules that react with the myosin heads and pull them back to their resting position, restarting the cycle (1) (see Figure 17-15, A). This sequence of events, known as cross-bridge cycling, repeats many times per second and continues as long as ATP molecules are produced and available. Relaxation of the muscle occurs when the nerve impulse ceases; sarcoplasmic reticulum rapidly pumps Ca⁺⁺ back into its storage sites. When calcium ions leave TnC, the entire troponin complex undergoes a conformational change, which moves tropomyosin back to its blocking position.

Increased cytoplasm Ca⁺⁺ concentration increases the heart’s force of contraction. The opposite occurs with decreased Ca⁺⁺ concentration or with drugs that block calcium ion entry into the muscle cell. This explains why calcium chloride (CaCl₂) is sometimes given to patients to improve the heart’s force of contraction.

Cardiac Muscle

Cardiac muscle differs from skeletal muscle in that individual muscle fibers are joined end-to-end to other fibers through junctions called intercalated disks (Figure 17-18). These disks are cell membranes (sarcolemma) separating individual cardiac muscle cells. That is, cardiac muscle is made up of many individual cells joined together in series. The electrical resistance through the intercalated disks is about one four-hundredth of the resistance through the outside muscle fiber membrane.² A reason for this low resistance is that cell membranes fuse at places along the disks, forming so-called gap junctions, which allow free passage of ions between cells. Functionally, the entire cardiac muscle mass acts as a single muscle fiber; for this reason, the myocardium is known as a syncytium.² If one fiber in the syncytium contracts, all fibers contract (“all-or-none” principle). The heart consists of two distinctly separate syncytia: the atrial syncytium and the ventricular syncytium. These two syncytia are electrically connected only by the AV bundle.

Frank-Starling Mechanism: Sarcomere Length–Dependent Activation

The inherent ability of the heart to increase its force of contraction as increasing amounts of blood flow into it is known as the Frank-Starling mechanism, named after two physiologists of the late nineteenth and early twentieth centuries.² Frank and Starling observed that the greater the diastolic volume of the heart, the greater the force of contraction. This phenomenon occurs in hearts removed from the body and is thus independent of neural mechanisms. The force of myocardial contraction is proportional to the rate of cross-bridge formation between actin and myosin filaments, which is influenced by the sarcomere’s length (length-dependent activation).⁴ The exact mechanism is incompletely understood. The traditional explanation is that myocardial stretch brings actin and myosin filaments into a more optimal degree of overlap for cross-bridge formation. Figure 17-19 shows that too much stretch disengages some cross-bridges, whereas extremely foreshortened fibers cause actin filaments to bypass one another and overlap. A more current view is that an increase in sarcomere length increases the sensitivity of TnC to calcium, which increases the rate of cross-bridge cycling.⁴ In addition, the passive recoil of stretched titin molecules also may contribute to increased contractile force; a combination of mechanisms is probably at work.⁴ Whatever the mechanism, a precontraction sarcomere length of about 2.2 µ is associated with the greatest force of contraction.⁴

The precontraction length of the cardiac muscle fiber is known as the heart’s preload. The clinician can measure ventricular preload by measuring ventricular filling pressure just before contraction (end-diastolic pressure). The assumption is that greater end-diastolic pressures stretch the muscle fibers to greater lengths. In clinical terms, the Frank-Starling mechanism states, “the greater the preload, the greater the force of contraction.” This statement is true only to a point because too much fiber stretch decreases the force of contraction (Figure 17-20).

Ventricular Filling (Preload)

As soon as the ventricles relax, the pressure that accumulated in the atria during ventricular contraction pushes the AV valves open, and blood rushes into the ventricles, creating a rapid filling phase (see Figure 17-21, f) and a slow filling phase (see Figure 17-21, g). As blood leaves the atria, atrial pressure decreases abruptly and is only slightly higher than ventricular pressure as blood continues to drain into the ventricles. During the last 0.1 second of ventricular filling time, the atria contract (atrial kick) and force an additional amount of blood into the ventricles, distending their walls slightly (see Figure 17-21, a). About 80% of ventricular filling is passive; the remaining 20% is caused by the atrial kick.² The atria are mere priming pumps for the ventricles, completing the “preloading” process.

Ventricular Emptying

Contraction of the ventricles rapidly builds up pressure, forcefully snapping the AV valves closed; this creates the first heart sound (see Figure 17-21, M₁ and b). A fraction of a second passes before the ventricular pressure increases enough to push the aortic and pulmonary semilunar valves open against the opposing aortic and pulmonary artery pressures. During this brief time, no blood leaves the ventricles (see isovolumetric contraction, Figure 17-21, b). The ejection period occurs immediately after aortic and pulmonary semilunar valves open (see Figure 17-21, AO); the resistance to this ejection is called afterload. Blood flow is rapid early in the ejection period, slowing as the ventricle ends its systolic phase (see Figure 17-21, c and d).

Ventricular Relaxation

As the ventricles relax, their pressures fall below the pressures of the aorta and pulmonary artery, causing aortic and pulmonary semilunar valves to snap shut, creating the second heart sound (see Figure 17-21, aortic closure). Closure of these valves abruptly stops backflow of blood into the ventricles, causing blood to rebound and send shock waves back into the aorta and pulmonary artery. Consequently, these elastic vessels dilate slightly and then recoil back to their original shapes. This vascular recoil helps push the blood forward in the arteries during ventricular diastole, creating the dicrotic notch in the aortic and pulmonary artery pressure waveforms (see aortic pressure dashed line in Figure 17-21, immediately after aortic valve closure).

A fraction of a second passes before ventricular pressures decrease enough to allow AV valves to open again. This time period is called isovolumetric relaxation (see Figure 17-21, e). Passive ventricular filling then begins, and the cycle is repeated.

The end-diastolic volume of each ventricle is about 110 to 120 mL.² Contraction ejects about 70 mL of blood (stroke volume), leaving behind about 40 to 50 mL (end-systolic volume). The filled ventricles normally eject about 60% of their volume (ejection fraction). A low ejection fraction (<50%) indicates poor contractility and pumping failure. Very powerful contractions during exercise can increase the ejection fraction to about 90%.²

Sympathetic and Parasympathetic Stimulation

Strong sympathetic stimulation can increase the heart rate from a normal 70 beats per minute to about 180 to 200 beats per minute and can double the force of contraction, resulting in a cardiac output two or three times greater than when at rest.² Drugs that mimic sympathetic stimulation (catecholamines) have the same effect. Drugs that block sympathetic activity have the opposite effect. Sympathetic activity is increased during exercise and anxiety. Inhibition of sympathetic activity decreases heart rate and force of contraction and can reduce cardiac output by as much as 30% below normal.²

Parasympathetic (vagal) stimulation primarily affects the atria, slowing the heart rate and, to a lesser extent, decreasing the force of contraction. Strong vagal stimulation causes severe bradycardia (slow heart rate) and can cause momentary cardiac arrest; however, the ventricles, which have much less vagal innervation than the atria, usually “escape” the influence of the atria and set up a rhythm of their own at a rate of about 20 to 40 contractions per minute.² The trachea is richly supplied with vagal nerves. For this reason, the common respiratory care practice of inserting a catheter into the trachea to remove accumulated secretions may stimulate severe bradycardia or momentary cessation of the heartbeat.

Effect of Heart Rate

An increased heart rate generally increases cardiac output, but this effect is limited when heart rate exceeds 170 to 220 beats per minute.² Above this critical range, diastolic time becomes so short that blood flow from the atria does not have enough time to fill the ventricles completely. The volume of blood the ventricles can eject with each stroke is reduced, offsetting the increase in cardiac output that normally accompanies increased heart rate.

Venous Reservoir

Because of their distensibility, the veins contain by far the greatest proportion of the blood volume at any given time (Table 17-1). Veins are an important blood reservoir, containing about 64% of the total blood volume. When large amounts of blood are lost from the body, reflex sympathetic venous constriction shifts blood into the arterial system. This compensatory venous constriction allows essentially normal circulatory function, even after 20% of the total blood volume is lost.²

The veins manage to return blood to the heart against the force of gravity through four basic mechanisms: (1) muscular “milking” of leg veins containing one-way valves; (2) sympathetic venous constriction; (3) cardiac pumping action, creating a “cardiac suction”; and (4) subatmospheric intrathoracic pressures during breathing. The normal subatmospheric pressure within the chest cavity aids venous return because abdominal venous pressure is positive.

Mean Arterial Pressure

Mean arterial pressure (MAP) is not simply the average of systolic and diastolic pressures as implied in Figure 17-25. The heart remains in systole for about one third of the cardiac cycle duration; thus, the arteries are exposed to the systolic pressure one third of the time and the diastolic pressure two thirds of the time. MAP is roughly estimated by the following equation:

< ?xml:namespace prefix = "mml" />MAP=(Systolic pressure+2[diastolic pressure])/3

An arterial systolic blood pressure of 120 mm Hg and diastolic pressure of 80 mm Hg (i.e., 120/80) yields an MAP of:

MAP=120+2(80)/3MAP=93.3mm Hg

The MAP is simply the average driving pressure that propels blood from the left ventricle to right atrium. MAP is closely related to overall adequacy of tissue perfusion in the body. The previous calculation is an estimate only; accurate measurement of MAP requires integration of the arterial pressure waveform.

The greatest fall in MAP occurs across the high-resistance arterioles: blood pressure is 85 mm Hg on entering the arterioles and 35 mm Hg on exiting them (see Figure 17-25). The reason for this large fall in MAP is that the arterioles offer the greatest resistance of any circulatory component. Flow across a resistance always produces a drop in pressure; the greater the resistance, the greater the pressure drop downstream from the site of resistance.

Systemic Vascular Resistance

Vascular resistance is measured as units of pressure required to produce a flow of 1 L per minute (mm Hg/L/min) through the vessels. To calculate SVR, one must measure the pressure gradient across the systemic circulation and the blood flow rate (cardiac output). The pressure across the systemic vasculature is equal to the MAP minus the right atrial pressure (RAP); after measuring cardiac output (CO), we calculate SVR as follows:

SVR=(MAP−RAP)/CO

Assuming MAP of 100 mm Hg, RAP of 0 mm Hg, and CO of 5 L/min, SVR is:

SVR=(100−0)/5SVR=20mm Hg/L/min

The SVR is a measure of the average resistance against which the left ventricle must work to eject the stroke volume; thus, SVR is an indicator of left ventricular afterload. (See Chapter 20 for a more thorough discussion of SVR measurement and its conversion to centimeter-gram-second or CGS units.)

The hematocrit (percentage of the blood volume composed of cells) also affects vascular resistance. The greater the number of cells, the greater is the friction between successive layers of blood (i.e., the greater is the blood’s viscosity). As blood hematocrit or viscosity increases, the heart must pump more forcefully to maintain the blood flow rate; that is, a higher pressure gradient is required to produce the same blood flow. This increases the numerator of the SVR equation, yielding a greater SVR value.

Blood Flow Rate and Velocity

Blood flow rate is determined by two factors: (1) driving pressure (pressure difference between two ends of a vessel) and (2) vascular resistance. This is simply a rearrangement of the SVR equation:

Blood flow=Driving pressure/resistanceCO=(MAP−RAP)/SVR

For a given driving pressure, an increased resistance decreases blood flow.

An increased peripheral or arteriolar resistance does not always decrease the blood flow (cardiac output) however. Arteriole constriction does decrease arteriole outflow or “arteriole runoff” into the capillaries, but it also increases pressure in the larger arteries and aorta. Increased arterial pressure offsets the increased vascular resistance, and blood flow may remain constant (see the previous equation). This kind of an increase in arterial blood pressure increases blood flow to organs not affected by arteriolar constriction. This is an important protective mechanism in shock caused by acute blood loss; reflex sympathetic stimulation causes peripheral vasoconstriction, maintaining arterial blood pressure and redirecting blood flow to vital central (“core”) organs, such as the heart, kidneys, lungs, liver, and brain. However, if the heart fails to increase its contractile force in the face of increased vascular resistance, blood flow decreases.

Although total blood flow rate throughout the vasculature is fairly constant under steady-state conditions, blood velocity is not constant. Velocity refers to the speed with which blood flows, or distance traveled per minute. Velocity is distinct from flow rate; flow rate is volume moved per minute. Given a constant blood flow rate, velocity is determined by the summative cross-sectional area of the vascular components. For example, the aorta’s cross-sectional area is about 5 cm², and the millions of capillaries have a combined cross-sectional area of about 2500 cm². For a cardiac output of 5 L per minute, blood velocity in the aorta is very high, but blood velocity in capillaries is very low (Figure 17-26). For this reason, aortic blood flow is normally turbulent, whereas capillary blood flow is laminar.

Turbulent flow vibrates the vessel walls, transmitting sound to the surface of the body. Abnormal vessel narrowing causes turbulent flow, which may be detected by a stethoscope. The swirling eddy currents of turbulent blood flow in partly obstructed arteries (e.g., arteries partially blocked by arteriosclerotic plaque) increase the probability of blood clot formation.

Hypertension

Hypertension, or high blood pressure, usually refers to a MAP greater than 110 mm Hg at rest; this coincides with a diastolic pressure of about 90 mm Hg and a systolic pressure of about 135 to 140 mm Hg.² The detrimental effects of hypertension occur in three major ways:² (1) excessive workload on the heart, leading to heart failure; (2) rupture of a major blood vessel in the brain, known as a stroke or cerebrovascular accident (CVA); and (3) multiple kidney hemorrhages leading to extensive renal tissue destruction.

Chronically high systolic pressures are associated with a stiffening, noncompliant arterial system, as occurs with old age and atherosclerosis (commonly known as “hardening of the arteries,” secondary to endothelial inflammation and buildup of fatty substances under the endothelium in the vessel wall). A high systolic pressure per se is not always abnormal. Systolic pressure naturally increases during exercise as stroke volume increases and more blood flow is needed. A high systolic pressure with a normal diastolic pressure means that peripheral vascular resistance is normal. That is, normally vascular resistance is low enough so that the peak pressures during systole fall to normal values during diastole.

An elevated diastolic pressure is a more serious sign of high SVR. As explained in the previous section, high peripheral resistance decreases the arteriole runoff rate—the rate at which blood

flows from the arterioles into the capillary beds. High arteriolar resistance slows the rate at which the peak pressure achieved during systole falls during diastole; this causes diastolic pressure to be higher than normal when the next ventricular contraction occurs. In the end, systolic pressure and MAP also increase.

About 90% of all people with hypertension have essential hypertension, or hypertension of unknown origin.² The peripheral vascular resistance in these individuals is about 40% to 60% above normal, about the same amount that MAP is increased.

Peripheral Venous Pressure

Peripheral venous pressure is not affected by RAP until it increases to about 6 mm Hg.² At that pressure, the veins are distended enough that their pressures rise with further RAP increases. Pumping failure of the heart—congestive heart failure—is a major reason for the elevation of venous pressure. If systemic venous pressure rises high enough, it may be transmitted back into the capillary beds and force fluid out into interstitial spaces. This kind of fluid accumulation on the venous side of systemic capillary beds is known as peripheral edema and is a sign of right ventricular failure. In such cases, structures upstream from the right atrium (jugular veins, liver, abdominal viscera, leg veins) become engorged with dammed-up blood and swell. These events result in jugular venous distention (JVD), hepatomegaly (enlarged liver), ascites (fluid accumulation in the abdominal cavity), and pedal edema (edema of the ankles and feet).

Normal peripheral venous pressures are affected by gravitational forces. Beginning at the right atrium, where pressure is about 0 mm Hg, venous pressure increases to about 22 mm Hg in the lower abdominal cavity, to 40 mm Hg in the femoral veins, and to 90 mm Hg in the feet.² (These pressures apply to an adult standing perfectly still.) Thus, a gradient normally exists for venous blood return to the heart.

Local Control

Blood flow varies widely from organ to organ depending on the organ’s metabolic needs or its functional purpose. Table 17-3 summarizes the blood flow to different organs. Generally, the higher the metabolic rate of the tissue, the greater its blood flow. Per gram of tissue weight, glandular structures receive a very high blood flow (see Table 17-3); likewise, the kidneys receive a high blood flow relative to their mass. High renal flow is necessary to cleanse the blood of waste products.

Two theories for the local regulation of blood flow are the vasodilator theory and the oxygen demand theory.² According to the vasodilator theory, as tissues become more metabolically active, they produce a vasodilator substance that dilates precapillary sphincters and arterioles. Various substances, including carbon dioxide, adenosine, lactic acid, nitric oxide, potassium ions, hydrogen ions, and phosphate compounds, cause vasodilation; the concentrations of these substances increase with increases in metabolic rate. Adenosine has been suggested as the most important of these local vasodilators; this substance is especially important in dilating coronary arteries in response to increased myocardial oxygen demand.² Endothelial nitric oxide is also an important substance in regulating local vascular resistance. Controlled release of nitric oxide from the vascular endothelium is responsible for maintaining a continuous state of vasodilation.^7,8 In the presence of hypoxemia, endothelial cells release more nitric oxide, promoting vasodilation.⁸

The oxygen demand theory is not much different than the vasodilator theory; it states that a lack of oxygen and other nutrients dilates precapillary sphincters and arterioles, causing local blood flow to increase. When adequate amounts of oxygen and nutrients are restored to the tissues, precapillary sphincters close again. For this reason, blood flow through capillaries is not continuous; rather, it is cyclic, fluctuating because precapillary sphincters periodically relax and contract. The duration of the open phases of the cycle is proportional to oxygen requirements of the tissues. This cyclic opening and closing of precapillary sphincters is called vasomotion.²

The same mechanisms responsible for vasomotion are responsible for autoregulation of blood flow. Arterial blood pressure can range from 75 to 175 mm Hg, but blood flow through tissues remains fairly constant. Even at minimum blood pressures, tissue perfusion can be maintained by local vasodilator mechanisms.

Central Control

Central neural control of the vascular system is mediated mainly through the autonomic nervous system, especially the sympathetic division. Sympathetic stimulation may cause either vasoconstriction or vasodilation, depending on which adrenergic receptor is stimulated. Adrenergic receptors respond to the sympathetic fiber’s release of norepinephrine (noradrenaline). The β₂-adrenergic receptors mediate vasodilation, and the α-adrenergic receptors mediate vasoconstriction.

Nervous control is responsible for shifting blood flow from one large area of the peripheral circulation to another. In severe blood loss, neural mechanisms induce peripheral vasoconstriction, increasing the blood pressure in central vessels sufficiently to maintain perfusion of the brain and heart. This response is rapid, occurring within seconds.

The vasomotor center of the lower pons and upper medulla in the brain discharges a continuous low level of impulses to sympathetic vasoconstrictor fibers. This continuous low-level state of constriction is counterbalanced by vasodilator substances, which produces a resting vasomotor tone.² Sympathetic impulses also cause the adrenal gland (the adrenal medulla) to release epinephrine and norepinephrine into the blood. These hormones are carried by the circulation to various parts of the body where they exert influences on vessel diameter similar to direct sympathetic nervous stimulation.

Baroreceptor Reflex

Baroreceptors (also known as pressoreceptors) are special sensory fibers in the walls of large systemic arteries that are responsive to stretch. They are most numerous at the fork of the internal and external carotid arteries and in the aortic arch. When stretched by high blood pressures, carotid and aortic baroreceptors transmit impulses through the glossopharyngeal and vagus nerves to the brain’s vasomotor and cardioregulatory centers. In response, the vasomotor center causes vasodilation, and the cardioregulatory center slows the heart rate. Consequently, arterial blood pressure decreases. A sudden reduction in blood pressure decreases the normal baseline impulse frequency transmitted by the baroreceptors to the brain; this causes vasoconstriction and increased heart rate. Through these mechanisms, the baroreceptors maintain blood pressure in a narrow range on a minute-to-minute basis.² The baroreceptors are responsible for maintaining a fairly constant blood pressure in the head and upper body when a person abruptly changes body posture (e.g., standing up after lying down).

Renin-Angiotensin-Aldosterone, Antidiuretic Hormone, and B-Natriuretic Peptide Systems

Baroreceptors do not control blood pressure on a long-term basis; they reset to any new blood pressure within 1 to 2 days.² Mechanisms that play important roles in long-term blood pressure regulation involve the kidney and include the renin-angiotensin-aldosterone system (RAAS), the vasopressin mechanism, and a natriuretic peptide produced by ventricular walls.²

In the RAAS, low blood pressure stimulates specialized tubular cells in the kidneys to produce the enzyme, renin. Renin acts on a plasma protein to produce angiotensin I. Angiotensin I circulates through the body to the lungs; there, the pulmonary vascular endothelium produces angiotensin-converting enzyme (ACE), which acts on angiotensin I to produce angiotensin II. Angiotensin II is a powerful vasoconstrictor that increases blood pressure significantly. Angiotensin II also increases blood pressure in another way; it causes the adrenal cortex to secrete aldosterone, which acts on the kidney tubules to increase their reabsorption of sodium ions and consequently water. The overall effect is an increased circulating blood volume and pressure. The RAAS is important in maintaining blood pressure in cases of circulatory shock.

In the vasopressin mechanism, a fall in blood pressure stimulates hypothalamic neurons in the brain to transmit impulses to the pituitary gland, stimulating the production of vasopressin, also known as antidiuretic hormone (ADH). ADH acts directly on blood vessels as a vasoconstrictor, but more importantly, it increases the kidney’s reabsorption of water by increasing the permeability of the distal tubules in the kidney. These mechanisms increase blood volume and blood pressure.

Ventricular cells of the heart release a hormone, B-type natriuretic peptide (BNP), in response to high blood pressure and stretch of ventricular walls.⁹ This hormone inhibits aldosterone and promotes sodium loss (diuresis) by the kidney and subsequently water loss, reducing blood volume and blood pressure. In this way, BNP inhibits the RAAS; it is an aldosterone antagonist. In congestive heart failure (pumping failure), the ventricles become distended, and their walls are stretched, increasing blood levels of BNP. (For this reason, increased blood levels of BNP are a diagnostic marker for heart failure and help differentiate cardiac and pulmonary causes of dyspnea.¹⁰) Increased blood BNP levels inhibit aldosterone, blocking sodium reabsorption and subsequently water reabsorption. In this way, diuresis occurs, and blood volume is reduced. However, when the heart fails to pump adequately, the body’s priority is to maintain the arterial blood pressure, and the fluid-retaining effects of the RAAS easily overwhelm the counteracting effects of increased BNP levels. The RAAS often causes too much fluid retention, which makes matters worse because it stresses the already failing heart even more. This harmful effect is only mildly lessened by increased blood levels of BNP.