As indicated previously, the arterial pressure is determined by the cardiac output and the total peripheral resistance. The total peripheral resistance is the total resistance in the entire systemic circulation which consists of many parallel circuits to major organs and tissues. The resistances in these individual circuits are not controlled in the same manner, and these resistances govern the distribution of cardiac output from the left ventricle into different regions of the body.


The following Table summarizes the normal blood flow and oxygen consumption in major organs and tissues under resting conditions. The blood flow through the splanchnic circulation (25% of cardiac output) can be subdivided into the hepatic arterial flow (7% of cardiac output) and the mesenteric-portal circulation (18% of cardiac output). The "Other Organs" include all parts of systemic circulations not specifically listed in the table, e.g., blood flow through the bones, many endocrine glands, urogenital system, bronchial circulation, etc. Because of the differences in sizes of the different organs, blood flow and oxygen consumption are also expressed in terms of values per 100 gm weight.

The function of blood flow is to transport materials to and from tissues. In many regions of the body, the main transport function is to meet the local metabolic demands. In several other regions, however, the primary purpose of the circulation is to provide a large flow rate for the processing of the physicochemical constituents of the blood, and the blood flow is in excess of that needed to meet the local metabolic demands. A calculation of the ratio of blood flow to oxygen consumption (B/O2) serves to distinguish these two types of purposes. The kidneys regulate the balance of water and solutes, the lungs regulate the blood gases, and the skin regulates heat balance. In these regions the ratio B/O2 is in excess of 70 ml/ml. The values for the lungs are not shown in the table, but here the large pulmonary blood flow (5,000 ml/min) is not concerned with gas exchange not local metabolic transport, which is met by the bronchial circulation. The blood flow and oxygen consumption in a given region determine the difference in O2 content between the arterial and venous blood (ΔA-VO2):

O2 = B (ΔA-VO2)

or     ΔA-VO2 = O2 /B

Therefore, the A-VO2 difference is inversely related to the B/ O2 ratio. Thus, the high B/O2 ratios in the renal and cutaneous circulations are associated with a low A-VO2 difference and hence a high venous O2 content.

In most other organs and tissues, the blood flow mainly serves to meet the local metabolic demand. In these regions the ratio B/O2 is less than 35 ml/ml, and the A-V O2 difference is higher than 3 cc/100 ml. The coronary circulation has the lowest B/O2 ratio, the largest A-V O2 difference and the lowest venous O2 content. These indicate that, in comparison to other regions, the myocardium has the least blood flow in relation to its metabolic requirement and that a large extraction of O2 from the blood is necessary to meet even the resting metabolic needs. This probably reflects the continuous activity of the cardiac muscle even under “resting” conditions. Whereas other organs can considerably increase their O2 extraction to meet enhanced metabolic requirements, this reserve is rather limited in the myocardium.


Blood Flow Oxigen Consumption Blood Flow     A-VO2 Venous O2
 %     ml   ml/min    %   cc   cc/min O2 Cons.     Content     Content
C.O. min 100 gm Total min 100 gm (ml/cc)     (ml/dl) (ml/dl)

1. Coronary   5    250    70   13    30    8.4     8       12.5   6.5
2. Cerebral  15   750    50   22    50    3.3    15        6.7   12.3
3. Splanchnic  25  1250   50   24    53    2.1    24        4.2   14.8
4. Renal  22  1100  400    7     15    5.5    73        1.4   17.6
5. Cutaneous   8    400    10    2      5     0.1    80        1.2   17.8
6. Muscular  17   850     2   27    60    0.2    14        7.1   11.9
7. Other regions   8    400     3     5     12    0.1     33        3.0   16.0
Total Systemic Circ. 100  5000   7  100   225  3.2    22        4.5   14.5

*These values are only round figures. They show considerable individual variation due to size and other factors. The venous O2 contents are calculated by using an arterial O2 content of 19 ml/dl.

Not shown in this table is the blood flow through the pulmonary circulation, which receives 100% of the cardiac output from the right ventricle, with pulmonary blood flow of approximately 200 ml/min/100 gm.

The values given in the table represent those obtained under resting conditions in a comfortable environment, and they can be altered significantly under a variety of conditions. For example, muscular exercise would increase markedly the blood flow and oxygen consumption in the exercising muscle. Exposure to a warm environment would increase the blood flow through the cutaneous circulation.


The blood flow (x through a given region x is determined by the pressure drop from arterial inflow to venous outflow (Pa-Pv) and the resistance in the region (Rx):

x  =  (Pa-Pv) / Rx

Since the values of Pa-Pv as well as the blood viscosity are essentially the same in most regions, x varies inversely with the vascular hindrance in each region. As discussed above, vascular hindrance is controlled by neurohumoral influences and by autoregulatory processes. The following table summarizes the type of adrenergic receptors (α or β) present in different regions, the primary effect of epinephrine, the presence or absence of sympathetic adrenergic and cholinergic innervation and the effect of stimulation, and autoregulatory control by metabolic (increased CO2 and acidity or reduced O2) and mechanical factors (increased transmural pressure).


Neurohumoral Influences                  
Adr.         Epi.           Symp.      N.S.
recep.      (prim.)       NE          ACh
Metabolic                         Mechanical
↑CO2, ↓pH       ↓O2               (↑P)

A. Systemic Circ.
  1. Coronary α , β           D             D              -      (D)                D
  2. Cerebral    -             -               -               -   D(CO2)           (D)               (C)
  3. Splanchnic
      a. Hepatic art.    α             C             C              -
      b. Mesent.-Port. α , β           C             C              -       D
  4. Renal    α             C             C              -                                                C
  5. Cutaneous α , β           C             C              -
  6. Muscular β*, (α)        D             C             D       D
B. Pulmonary Circ.   (α)           (C)          (C)             -       C
                                       (↓alv. pO2)

*β receptors in blood vessels of skeletal muscle are not innervated
  C: Constriction;   D: Dilatation

A comparison of the mechanisms controlling vascular hindrance in different regions indicate that vasoconstriction in response to sympathetic adrenergic influence occurs primarily in the abdominal visceral organs (splanchnic region and kidney), skeletal muscle and skin.The brain has no significant sympathetic adrenergic influence, whereas the coronary circulation responds to sympathetic adrenergic impulses by dilation. Therefore, reflex activation of the sympathetic adrenergic system causes a redistribution of blood flow, which is diverted away from the vasoconstricted areas and to the heart and the brain.

Autoregulation by metabolic factors plays an important role in the control of coronary blood flow (especially sensitive to hypoxia) and cerebral blood flow (especially sensitive to changes in PCO2). Autoregulation by mechanical factors also occurs in the cerebral circulation. Metabolic autoregulation is seen in the mesenteric and muscular circulations, and the mechanical type of autoregulation is observed in the renal circulation. Pulmonary circulation has limited sympathetic adrenergic innervation. The pulmonary vasculature can respond to a local reduction in alveolar PO2 by vaconconstriction, thus diverting pulmonary blood flow from poorly ventilated areas to other areas that are better ventilated.

The factors regulating cerebral blood flow, renal blood flow (lectures on the kydney) and pulmonary blood flow are be treated in greater detail elsewhere. In the following two subsections the factors controlling coronary blood flow and blood flow through the skeletal muscle will be discussed.


The coronary supply to the heart is equal to approximately 5% of the cardiac output under resting conditions. Of the total coronary flow approximately 85% is supplied by the left coronary artery and approximately 15% is supplied by the right coronary artery. The relative distribution of these two coronary arteries between the left and right ventricles varies among individuals. The coronary circulation contains a rich capillary network such that the number of capillaries is at least as large as the number of myocardial fibers. The outflow from the left ventricle generally drains into the coronary sinus which empties into the right atrium. The outflow from the right ventricular myocardium drains primarily via the anterior cardiac veins, which empty into the right atrium. There are also small amounts of venous blood collected by the Thebesian vessels that can drain into either the right or left chambers. Normally the coronary sinus outflow constitutes approximately 70% of the total venous drainage.


The external pressure on the coronary circulation exerted by the force of contraction of the myocardium has an important influence on coronary resistance, especially in the left ventricular myocardium. During each phase of the cardiac cycle this extravascular pressure changes, as does the aortic pressure. Since the coronary flow is determined by the ratio of the driving aortic pressure to the coronary resistance, the phasic variations in these two parameters result in a phasic change in coronary flow (see figure). During diastole (0), when the ventricular myocardium is relaxed, coronary flow depends primarily upon the aortic pressure. At the beginning of isovolumetric contraction (1), the extravascular pressure increases very sharply, resulting in a marked rise in coronary resistance, especially on the left side. Therefore, there is a marked decrease of the left coronary flow, such that the flow is stopped or even reversed. Following the opening of the aortic valve (2) the ejection of blood from the left ventricle reduces the extravascular pressure and coronary resistance. Since the aortic pressure is rising at the same time, these changes cause a rise in left coronary flow. During the period of reduced ejection (3), the coronary flow decreases together with aortic pressure.

With the onset of isovolumetric relaxation (4), the extravascular pressure decreases, and the resulting reduction in coronary resistance causes a rise in left coronary flow. Thereafter (5), the coronary flow changes in the same direction as the arterial pressure during diastole.

Because of the phasic nature of the left coronary arterial inflow and the relatively longer duration of diastole than systole, approximately 3/4 of the left coronary inflow occurs during diastole and only 1/4 during systole. Therefore, excessive changes in the heart rate, by changing the relative duration of diastole in the cardiac cycle, can affect left coronary flow.

The wall stress generated during ventricular contraction is the greatest on the subendocardial surface, and it decreases progressively toward the epicardial surface. Therefore, the compression of left coronary vessels is greater in the subendocardium, leading to a vulnerability of subendocardial coronary blood flow.

Because the contraction of the right ventricle is considerably weaker than that of the left ventricle, right coronary vessels are subject to much less extravascular compression during systole. The phasic tracing of right coronary blood flow follows more closely the contour of the aortic pressure tracing and resembles the flow pattern in other regions of the body.

The variations in extravascular pressure in the coronary circulation also affect the capacity of the veins and the volume of blood in the venous side of the coronary circulation. During the contraction phase as the ventricular pressure increases, the size of the veins is reduced and blood is squeezed out of the veins in the coronary circulation. As relaxation begins and ventricular pressure drops, there follows an expansion of the coronary veins and a reduction in venous outflow.


Oxigen. Under normal resting conditions the coronary circulation extracts a large percentage of the oxygen delivered by the arterial supply (see Table on Blood Flow and Oxygen Consumption at Rest). A reduction in coronary flow tends to cause a corresponding reduction in myocardial PO2, since the A-V oxygen difference cannot be increased much further. Decreases in myocardial PO2 exert a strong vasodilation influence on the coronary circulation, and this constitutes the major autoregulatory mechanism of coronary flow.

Carbon dioxide and pH. An increase in PCO2 or decrease in pH causes vasodilation, but the effect is less pronounced than that produced by a lowering of PO2.


Both sympathetic stimulation and catecholamines cause coronary vasodilation. They do it indirectly, however, since the direct effect of sympathetico-adrenal stimulation is vasoconstriction due to the greater preponderance of α receptors over β receptors in the coronary vessels. Sympathetic activation stimulates myocardial contractility; it is the metabolic changes that result from this stimulation and that cause the vasodilation via autoregulation.

Vagal stimulation has two conflicting effects on the coronary vessels. It causes vasoconstriction via direct stimulation of the vessel’s smooth muscle, but vagal stimulation also stimulates the coronary endothelium to release EDRF (Endothelium Derived Relaxing Factor) which relaxes coronary smooth muscle cells. The net effect of vagal stimulation is a slight vasodilation, but the effect probably has little physiological significance.


The skeletal muscle comprises more than one half of the total body weight, but it receives only approximately 17% of the cardiac output and uses only approximately 27% of the total oxygen consumed at rest. During muscular exercise, the vasodilation and opening of previously non-circulating vessel cause marked increases in muscle blood flow and oxygen consumption. The variations in blood flow and oxygen consumption are much larger in the skeletal muscle than in other tissues and organs. Blood vessels in the skeletal muscle are regulated by many different neural and humoral factors, and their control is probably the most complicated among the various regional circulations (see Figure).


The skeletal muscle vessels contain both α and β adrenergic receptors. The α receptors are innervated by sympathetic adrenergic nerves. The activation of sympathetic adrenergic system following hemorrhage, hypoxemia, or exposure to cold causes the release of norepinephrine, which combines with the α receptors to constrict skeletal muscle vessels. The β receptors in the skeletal muscle vessels are more abundant than the α receptors. The β receptors in the skeletal muscle are not innervated, however, and therefore respond only to the blood-borne catecholamines secreted by the adrenal medulla or administered therapeutically. When catecholamines bind to the β receptors of skeletal muscle vessels, the vessels dilate. Due to the greater abundance of β receptors, the blood borne catecholamines, especially epinephrine, cause vasodilation in the skeletal muscle.


In addition to the α and β adrenergic receptors, skeletal muscle vessels also contain the γ cholinergic receptors which are innervated by the sympathetic cholinergic nerves. As shown in the following diagram, the sympathetic cholinergic nerves are under the influence of the cerebral cortex and the hypothalamus. The combination of the acetylcholine released at the postganglionic nerve endings with the γ receptors causes vasodilation of the skeletal muscle. This system is activated by anticipation of exercise and by emotional stimuli, e.g., the sight of blood, and the resulting sudden vasodilation in the skeletal muscle may cause significant reductions in arterial pressure and cerebral blood flow, leading to fainting.


The accumulation of CO2 and acid metabolites and the reduction in PO2 cause vasoldilation in the skeletal muscle. This is the most important factor causing muscular vasodilation during exercise, leading to increases in skeletal muscle blood flow by a much as 20-25 fold and increases in oxygen consumption of more than 40 fold.