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 locally produced factors.

Among the most important of the humoral factors that affect circulatory function are the following:

Vasoconstrictor Agents

Norepinephrine and Epinephrine: Norepinephrine is an especially powerful vasoconstrictor hormone; epinephrine is less so and in some tissues even causes mild vasodilation. (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 exercise, 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 epinephrine into the blood. These hormones then circulate to all areas of the body and cause almost the same effects on the circulation as direct sympathetic stimulation, 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 vasoconstrictor 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 arterial pressure.

Vasopressin: Vasopressin, also called antidiuretic hormone, is even more powerful than angiotensin II as a 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.

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 called antidiuretic hormone.

Vasodilator Agents

Bradykinin: Several substances called kinins cause powerful 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 particular 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 maceration 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 immediately on alpha2-globulin to release a kinin called kallidin that is then converted by tissue enzymes into bradykinin. Once formed, bradykinin persists for only a few minutes because it is inactivated by the enzyme carboxypeptidase or by converting enzyme, the same enzyme 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 arteriolar dilation and increased capillary permeability. For instance, 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.

Histamine: Histamine is released in essentially every tissue 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.

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 general effect of calcium to stimulate smooth muscle contraction.

2. An increase in potassium ion concentration, within the physiological range, causes vasodilation. This results from the ability of potassium 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 blood vessels 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.

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