17. Local and humoral control of tissue blood flow

Factors inducing angiogenesis - which

- Vascular endothelial growth factor (VEGF) - Fibroblast growth factor - Angiogenin These have been isolated from tissues with inadequate blood supply, suggesting it's the lack of nutrients that induces angiogenesis.

Nitric Oxide (NO) as a vasodilator

Endothelial cells has NOS that synthesizes NO from arginine and oxygen. NO acts on local tissues by activating a cyclase producing cGMP, which relaxes vascular smooth muscles. When blood flow causes stress on the endothelial cells in the vessel wall, NO is produced. It can also be stimulated by angiotensin II, protecting from too much vasoconstriction.

Circulation control - Histamine

Histamine is a powerful vasodilator, and increases capillary permeability. Histamine is released anywhere there is tissue damage or an allergic reaction. Histamine comes from mast cells in tissues, and basophils in blood.

Circulation control - Norepinephrine and epinephrine

Norepinephrine is a powerful vasoconstrictor, epinephrine less so. It's released in response to sympathetic stimulation, providing a dual control system - both direct nerve stimulation and hormonal effect in circulating blood.

Local blood flow - Long-term control

Slow, controlled changes in flow over a period of days, weeks, or months. Done by an increase or decrease in the physical sizes and numbers of actual blood vessels supplying the area.

Preventing the degradation of cGMP in vasodilation

Some medication inhibits the degradation of cGMP by PDE-5, allowing NO to work for longer and prolonging vasodilation. The main use of PDE-5 is to treat erectile dysfunction.

Relationship between metabolism and blood flow

An increase in metabolism up to 8 times normal increases the blood flow acutely about fourfold.

Angiogenesis in blood flow

Angiogenesis - the development of new blood vessels. If the metabolism in a tissue is increased for a prolonged period, vascularity increases.

Oxygen in long-term regulation of blood flow

Animals in high altitudes have increased vascularity, while neonates bathed in oxygen will stop making vessels in the retina. When the infant is taken out, there is explosive growth of the retinal vessels, and sometimes there is overgrowth to the extent that it causes blindness - called retrolental fibroplasia.

Nutrient lack theory for local blood flow control

As oxygen and other nutrients are needed for vasoconstriction, they would naturally dilate when there is a lack of nutrients. The precapillary sphincters open cyclically, this could be explained by available oxygen making them able to close, and then they dilate when the oxygen is used, to allow blood flow and again new oxygen.

Humoral control of the circulation - what does it mean

It means control by substances secreted or absorbed into the body fluids - such as hormones and locally produced factors. The may affect the entire body or only locally.

Adenosine in vasodilation

Many physiologists believe that adenosine is the most important substance for increased blood flow from vasodilation. The heart releases adenosine to dilate the coronary arteries. It also fits as during low blood flow, the cells use ATP, releasing adenosine. It is probably a combination of several substances.

Tubuloglomerular feedback in the kidneys

Blood flow control in the kidneys is largely this feedback. The composition of the fluid in the early distal tubule is detected by an epithelial structure of the tubule, called the macula densa. This is located where the distal tubule lies adjacent to the afferent and efferent arterioles at the nephron juxtaglomerular apparatus. When too much fluid is filtering, the macula densa notifies the afferent arteriole, reducing blood flow and glomerular filtration.

Endothelin

Endothelin is a powerful vasoconstrictor also released by the endothelial cells. It's usual stimulus is damage to the endothelium, shutting down bleeding from arteries as big as 5 mm in diameter when they are broken. Drugs that block endothelin have been used to treat pulmonary hypertension.

Circulation control - Angiotensin II

This is powerful vasoconstrictor, 1/1mill gram can increase the arterial pressure by 50 mm Hg. It's effect is to powerfully constrict small arterioles, often over large areas, increasing the total peripheral resistance and thereby increasing arterial pressure.

The metabolic theory of autoregulation of blood flow

This theory fits with the theories of control of blood flow. When the arterial pressure rises, the blood flow increases and flushes out the vasodilators released by the tissues. These nutrients then cause the sphincters etc to constrict and the flow to return to normal.

The myogenic theory of autoregulation of blood flow

This theory is based on the observation that a sudden stretch of small blood vessels results in the smooth muscles of the vessels to contract. Thus, an increase in pressure will stretch the vessels, eliciting the contraction response, and decreasing blood flow.

Circulation control - Vasopressin

Vasopressin is a vasoconstrictor even more powerful than Angiotensin II, but is believed not to be used as that except after severe hemorrhage. It is also a antidiuretic, increasing greatly water reabsorption from the renal tubules back into the blood.

Active hyperemia

When a tissue becomes highly active, such as a muscle or a GI gland, local blood flow increases to meet the nutritional needs.

Reactive hyperemia

When blood supply to a tissue has been blocked for some time and then unblocked, there is a period of increased blood flow to the area, proportional to how long it was blocked. This is reactive hyperemia. The reactive hyperemia phase lasts long enough to repay almost exactly the tissue oxygen deficit that has accrued.

Autoregulation of blood flow during heightened arterial pressure

A rapid increase in arterial pressure will cause an immediate rise in blood flow in any tissue. But, within less than a minute, the blood flow returns to normal levels, even though the increased arterial pressure persists. This is autoregulation of blood flow. For pressures going between 70 ->175 mm Hg, blood flow increases only 20-30% even though arterial pressure increases 150%.

Vasodilator theory for acute local blood flow

According to this theory, the greater the rate of metabolism or the less the availability of oxygen or some other nutrients, the greater the rate of formation of vasodilator substances in these cells. Suggested substances include adenosine, CO2, histamine, K+, H+.

Local blood flow - acute control

Achieved by rapid changes in local vasodilation or -constriction of the arterioles, metarterioles, and capillary sphincters. The effect is within seconds or minutes to provide rapid maintenance and proper blood flow.

Ions controlling local circulation

Calcium - vasoconstriction from smooth muscle stimulation. Potassium - vasodilation from inhibition of smooth muscle. Magnesium - powerful vasodilation from inhibition of smooth muscle. Hydrogen ion - increase causes dilation, and decrease causes constriction. Acetate and citrate - cause vasodilation. CO2 - causes vasodilation, especially in the brain.

Circulation control - Bradykinin

The kinins can cause powerful vasodilation. Kallikrein is a proteolytic enzyme that is stimulated by inflammation etc, and makes kinins by breaking off parts of alpha2-globulins. Bradykinin causes powerful arteriolar dilation and increased capillary permeability. It controls capillary leakage and regulates blood flow in skin, salivary and GI glands.