Humoral Control of the Circulation

Humoral Control of the Circulation

Humoral control of the circulation means control by substances secreted or absorbed into the body fluids— such as hormones and ions. Some of these substances are formed by special glands and transported in the blood throughout the entire body. Others are formed in local tissue areas and cause only local cir-culatory effects. Among the most important of the humoral factors that affect circulatory function are the following.

Vasoconstrictor Agents

Norepinephrine and Epinephrine. Norepinephrineis anespecially powerful vasoconstrictor hormone; epi-nephrine is less so and in some tissues even causes mildvasodilation. (A special example of vasodilation caused by epinephrine occurs to dilate the coronary arteries during increased heart activity.)

When the sympathetic nervous system is stimulated in most or all parts of the body during stress or exer-cise, the sympathetic nerve endings in the individual tissues release norepinephrine, which excites the heart and contracts the veins and arterioles. In addition, the sympathetic nerves to the adrenal medullae cause these glands to secrete both norepinephrine and epi-nephrine into the blood. These hormones then circu-late to all areas of the body and cause almost the same effects on the circulation as direct sympathetic stimu-lation, thus providing a dual system of control: (1) direct nerve stimulation and (2) indirect effects of norepinephrine and/or epinephrine in the circulating blood.

Angiotensin II. Angiotensin II is another powerful vaso-constrictor substance. As little as one millionth of a gram can increase the arterial pressure of a human being 50 mm Hg or more.

The effect of angiotensin II is to constrict powerfully the small arterioles. If this occurs in an isolated tissue area, the blood flow to that area can be severely depressed. However, the real importance of angiotensin II is that it normally acts on many of the arterioles of the body at the same time to increase the total peripheral resistance, thereby increasing the arte-rial pressure. Thus, this hormone plays an integral role in the regulation of arterial pressure.

Vasopressin. Vasopressin, also calledantidiuretichormone, is even more powerful than angiotensin II asa vasoconstrictor, thus making it one of the body’s most potent vascular constrictor substances. It is formed in nerve cells in the hypothalamus of the brain  but is then transported downward by nerve axons to the posterior pituitary gland, where it is finally secreted into the blood.

It is clear that vasopressin could have enormous effects on circulatory function. Yet, normally, only minute amounts of vasopressin are secreted, so that most physiologists have thought that vasopressin plays little role in vascular control. However, experiments have shown that the concentration of circulating blood vasopressin after severe hemorrhage can rise high enough to increase the arterial pressure as much as 60 mm Hg. In many instances, this can, by itself, bring the arterial pressure almost back up to normal.

Vasopressin has a major function to increase greatly water reabsorption from the renal tubules back into the blood, and therefore to help control body fluid volume. That is why this hormone is also calledantidiuretic hormone.

Endothelin—A Powerful Vasoconstrictor in  Damaged  Blood Vessels. Still another vasoconstrictor substance thatranks along with angiotensin and vasopressin in its vasoconstrictor capability is a large 21 amino acid peptide called endothelin, which requires only nanogram quantities to cause powerful vasoconstric-tion. This substance is present in the endothelial cells of all or most blood vessels. The usual stimulus for release is damage to the endothelium, such as that caused by crushing the tissues or injecting a trauma-tizing chemical into the blood vessel. After severe blood vessel damage, release of local endothelin and subsequent vasoconstriction helps to prevent exten-sive bleeding from arteries as large as 5 millimeters in diameter that might have been torn open by crushing injury.

Vasodilator Agents

Bradykinin. Several substances calledkininscause pow-erful vasodilation when formed in the blood and tissue fluids of some organs.

The kinins are small polypeptides that are split away by proteolytic enzymes from alpha2-globulins in the plasma or tissue fluids. A proteolytic enzyme of par-ticular importance for this purpose is kallikrein, which is present in the blood and tissue fluids in an inactive form. This inactive kallikrein is activated by macera-tion of the blood, by tissue inflammation, or by other similar chemical or physical effects on the blood or tissues. As kallikrein becomes activated, it acts imme-diately on alpha2-globulin to release a kinin called kallidin that then is converted by tissue enzymes into bradykinin. Once formed, bradykinin persists for onlya few minutes because it is inactivated by the enzyme carboxypeptidase or by converting enzyme, the sameenzyme that also plays an essential role in activating angiotensin. The activated kallikrein enzyme is destroyed by a kallikrein inhibitor also present in the body fluids.

Bradykinin causes both powerful arteriolardilation and increased capillary permeability. Forinstance, injection of 1 microgram of bradykinin into the brachial artery of a person increases blood flow through the arm as much as sixfold, and even smaller amounts injected locally into tissues can cause marked local edema resulting from increase in capillary pore size.

There is reason to believe that kinins play special roles in regulating blood flow and capillary leakage of fluids in inflamed tissues. It also is believed that bradykinin plays a normal role to help regulate blood flow in the skin as well as in the salivary and gastroin-testinal glands.

Histamine. Histamine is released in essentially everytissue of the body if the tissue becomes damaged or inflamed or is the subject of an allergic reaction. Most of the histamine is derived from mast cells in the damaged tissues and from basophils in the blood.

Histamine has a powerful vasodilator effect on the arterioles and, like bradykinin, has the ability to increase greatly capillary porosity, allowing leakage of both fluid and plasma protein into the tissues. In many pathological conditions, the intense arteriolar dilation and increased capillary porosity produced by histamine cause tremendous quantities of fluid to leak out of the circulation into the tissues, inducing edema. The local vasodilatory and edema-producing effects of histamine are especially prominent during allergic reactions.

Vascular Control by Ions and Other Chemical Factors

Many different ions and other chemical factors can either dilate or constrict local blood vessels. Most of them have little function in overall regulation of the circulation, but some specific effects are:

1.     An increase in calcium ion concentration causes vasoconstriction. This results from the generaleffect of calcium to stimulate smooth muscle contraction.

2.     An increase in potassium ion concentration causes vasodilation. This results from the ability ofpotassium ions to inhibit smooth muscle contraction.

3.     An increase in magnesium ion concentration causes powerful vasodilation because magnesium ions inhibit smooth muscle contraction.

4.      An increase in hydrogen ion concentration (decrease in pH) causes dilation of the arterioles.

Conversely, slight decrease in hydrogen ion concentration causes arteriolar constriction.

5.     Anions that have significant effects on bloodvessels are acetate and citrate, both of which cause mild degrees of vasodilation.

6.     An increase in carbon dioxide concentration causes moderate vasodilation in most tissues, but marked vasodilation in the brain. Also, carbon dioxide in the blood, acting on the brain vasomotor center, has an extremely powerful indirect effect, transmitted through the sympathetic nervous vasoconstrictor system, to cause widespread vasoconstriction throughout the body.