Local Control of Blood Flow

Active Hyperemia

Increase in blood flow to an organ or tissue due to an increase in metabolism (e.g., active muscles during exercise).

Prostaglandins

Prostaglandins are part of a large family of arachadonic acid metabolites, which can have both vasodilator and vasoconstrictor activities. For example, the F family of prostaglandins (PGFs) are mainly vasocontrictors whereas the E family (PGEs) are vasodilators

In occlusive muscle activity, such as lifting weights, what type of hyperemia is predominant?

Reactive hyperemia

Hyperemia

An increase in blood flow to different tissues of the body. In the absence of adequate blood flow (e.g., elevated metabolism, occluded blood flow), ions will accumulate. Low O₂ content (hypoxia), elevated CO₂ (hypercarbia), K⁺ (hyperkalemia), H⁺ (acidosis) and adenosise produce vasodilation. When blood flow is restored, the vessels are dilated and flow is elevated until the metabolites have been washed out.

Coronary Blood flow

Any increase in cardiac activity and myocardial O₂ consumption requires an immediate increase in blood flow, which is achieved via active hyperemia. Good autoregulation between 60 and 180 mmHg perfusion pressure also helps to maintain normal coronary blood flow whenever coronary perfusion pressure changes due to changes in aortic pressure. During conditions such as stress (flight of fight) or exercise, heart rate and stroke volume increases as a result of sympathetic nerve activity. However, activation of sympathetic nerves innervating the coronary vasculature causes only transient vasoconstriction mediated by α-1 receptors. This brief (and small) vasoconstrictor response is floowed by vasodilation due to active hyperemia caused by enhanced production of ADENOSINE (metabolite) and NITRIC OXIDE (myogenic regulation).

Mechanism of Myogenic control of blood flow

As a protective mechanism, when subjected to excessive stretch this opens a number of stretch-activated channels (including TRP cationic and ENaC channels and this depolarizes the muscle cells to ~40 mV, which activates L-type Ca channels inducing contraction (vasoconstriction)

Cerebral blood flow

As with coronary flow, local metabolic conditions are the preferred means of vascular control in the brain. Brain blood flow increases via *active hyperemia* when brain activity increases.

Describe left ventricular coronary blood flow during systole

Because Left ventricular muscle contracts with high force, during systole the coronary vessels are squeezed reducing flow to heart muscle. This leads to an increase in metabolic waste products which induces local vasodilation so blood flow during systole does increase.

Describe right ventricular coronary blood flow during systole

Because the right ventricular muscle does not contract with as much force, coronary vessels are not compressed as much during systole. Right coronary flow increases during systole because coronary artery pressure rises during systole and results in an increased driving pressure As a result there is reduced reactive hyperemia component on the right coronary arteries compared to left.

What type of muscle has the greater increase in blood flow during exercise?

Red muscle fibers (aerobic)

Why does coronary flow differ from many other organs?

It is pulsatile. Flow through the vessels varies during the course of the cardiac cycle due to compression that occurs during contraction.

Having a longer period of occlusion results in...?

Longer subsequent period of reactive hyperemia.

Metabolic control of blood flow

Metabolic regulation of blood flow utilizes mechanisms that originate from from the tissues that surround the blood vessels (i.e., metabolites and paracrine agents). Paracrine agents are produced locally, released locally, and act locally.

List the metabolites, paracrine, and other agents involved in metabolic control of blood flow.

Metabolites: Adenosine, Lactate, H⁺, K⁺ Paracrine agents: Ang II, Histamine, bradykinin, Prostaglandins (PGFs, constrict; PGEs, dilate) Other: ↓O₂, ↑CO₂ (produce local dilation)

Myogenic Control of Blood Flow

Myogenic regulation of blood flow utilizes mechanisms that originate within the blood vessels themselves (i.e., endothelial products (NO) and myogenic reflex control).

Nitric Oxide (Myogenic Regulation)

NO is formed within endothelial cells in response to elevation of the pressure gradient along the long axis of the vessel, i.e., increased "shear stress". Being a gas, it easily diffuses from endothelial cells to the underlying smooth muscles.

Unlike the coronary circulation, the primary metabolite controlling local flow in the brain appears to be...?

PCO₂ A raised arterial CO₂ (Hypercapnia) causes cerebral vasodilation whereas a reduced arterial CO₂ (e.g.,hyperventilation) leads to vasoconstriction and dizziness.

Endothelial NO production is stimulated by a variety of factors, some are:

Paracrine agents, such as, histamine (via H1 receptors) and bradykinin, as well as Acetylcholine from cholinergic nerves. Also, increased shear stress on the inner vessel wall.

Describe left ventricular coronary blood flow during diastole

Blood flow is greatest during diastole, because the ventricular muscle is relaxed and the coronary vessels are unobstructed. During diastole when the left ventricular muscle is relaxed, coronary vessels are open and coronary flow increases as a result of reactive hyperemia.

Increases sympathetic innervation has what effect in the brain?

Reduces blood flow to the brain due to vasoconstriction but this effect is only seen at higher arterial pressures

Mechanism of NO Myogenic Regulation

Shear stress and/or other factors (Ach, bradykinin, and histamine) leads to an increase in Ca within the endothelial cells. This activates NO synthase which ctalyzes the synthesis of NO from arginine to citrulline, generating NO which due to the fact it is a lipophillic gas, easily diffuses to the adjacent smooth muscle cells (half life is 6s). In smooth muscle cel NO activates a soluble Guanylate cyclase which catalyzes the breakdown of GTP to cGMP which activates various processes to relax the smooth muscle cells.

Myogenic vasoconstriction involves the following sequence of steps:

1. Increased intraluminal pressure 2. Stretch-induced smooth muscle depolarization 3. Opening of voltage-gated Ca²⁺ channels 4. Global increase in Ca²⁺ concentration 5. Myosin Light Chain phosphorylation This is an active process, independent of the endothelium and perivascular nerves. When Ca²⁺ is removed, the arteriole passively distends when subjected to the same pressure.

Autoregulatory range

60 to 180 mmHg. Increase (180) or decrease (60) to these levels will not alter blood flow.

Reactive Hyperemia

A short interruption of blood flow due to a temporary occlusion, which results in a build up of metabolic waste, causes vasodilation and increased blood flow.

In phasic activity, such as running, what type of hyperemia is predominant?

Active hyperemia

What metabolites are responsible for hyperemia in skeletal muscle blood flow?

Adenosine and K⁺

Coronary Blood flow and sympathetic activation

Coronary blood flow is controlled almost entirely by local factors. It is limited by SNS control because few α1 receptors are present. Sympathetic activation to the heart results in an overall coronary vasodialtion response and increased coronary blood flow due to increased metabolic activity (↑HR, ↑contractility) and myogenic activity (↑NO), despite direct vasoconstrictor effects of sympathetic activation on the coronaries

Histamine

Histamine is a paracrine involved in metabolic control of blood flow. Mast cells release histamine in response to tissue injury and allergic responses causing vasodilation and increased capillary permeability (e.g., exudated as in insect bite).

What are responsible for the control of blood flow in Active Hyperemia?

Precapillary sphincters in capillary beds

Myogenic theory of blood flow regulation (Myogenic Reflex)

Stretch of arteriolar and arterial vessel walls appears to alter ion channel activity (mechanosensitive channels), leading to depolarization and subsequent contraction. Thus when blood flow increases dramatically because of a large rise in blood pressure, the vessel wall is stretched. This elicits a contractile response reducing vessel diameter and returning flow towards normal values.

Autoregulation

The ability of an organ to maintain a constant blood flow when arterial pressure changes. Predominantly occurs in vessels within the heart, brain, and kidney.

Circle of Willis

The basilar artery and the internal carotids combine to form the Circle of Willis, forming a network of arteries that can maintain flow even with blockage of some of the major arteries.