Regulation of Organ Blood Flow Mark T Ziolo, PhD, FAHA Associate Professor, Physiology & Cell Biology 019 Hamilton Hall

Objectives Describe the regulation of organ blood flow by myogenic regulation and autoregulation (intrinsic tone, neuronal influence, local or metabolic influence, hormonal influence) Describe active and reactive hyperemia

Detailed Objectives  Understand the myogenic regulation and the autoregulation of blood flow  Know the mechanism of myogenic regulation  Know how the different factors (intrinsic tone, neuronal influence, local (metabolic) influence, and hormonal influence) responsible for autoregulation regulate blood flow  Understand the role of active and reactive hyperemia  Understand how control of flow is different between organs with strong local (metabolic) control of arterial tone and organs with strong neuronal control of arterial tone

References Mohrman DE, Heller LJ. Cardiovascular Physiology Seventh Edition. Lange Medical Books/McGraw-Hill Publishers, Berne RM, Levy MN. Cardiovascular Physiology Sixth Edition. Mosby-Year Book, Inc., MediaPhys 3.0. An Introduction to Human Physiology. The McGraw-Hill Publishers, 2010.

Myogenic Regulation

Vital Organ Myogenic Regulation

Vital Organ Pressure Myogenic Regulation

Vital Organ Pressure Myogenic Regulation

Autoregulation

Myogenic Regulation  Smooth muscle contracts in response to an increase in transmural pressure  Smooth muscle relaxes in response to a decrease in transmural pressure

Muscle Autoregulation- with ↑ metabolic demand

Muscle Working Autoregulation- with ↑ metabolic demand

Muscle Working Autoregulation- with ↑ metabolic demand

Autoregulation  Factors Responsible:  Intrinsic tone  Neuronal Influences  Local Influences  Hormonal Influences

Intrinsic Tone  Arterioles remain partially constricted even when all external influences are removed  This baseline is what external influences adjust

Neuronal Influences  Fibers innervate arterioles in ALL systemic organs  These fibers release NE proportionally to their electrical activity  Acts via  -adrenergic receptors  Increases vascular tone  Via decrease membrane potential & increase in AP frequency  Parasympathetic may act on the external genitalia for vasodilation

Local (metabolic) Influences  Smooth muscle is exposed to the chemical composition of the interstitial fluid of the organ  These substances reflect the balance of the organ’s metabolic activity and blood supply  O 2 *, CO 2, H +, K +, lactic acid, phosphate  adenosine * Pulmonary circulation

Tissue Cells Blood Flow Release proportional to tissue metabolism Vasodilator factors Removal rate proportional to blood flow Local (metabolic) Influences

Other Local Influences  Influences from Endothelial cells  Nitric oxide, endothelin  Other influences  Prostaglandins (COX pathway) Some vasodilate, others vasoconstrict  Histamine Vasodilation and increases permeability (swelling)  Bradykinin Vasodilation via nitric oxide

Hyperemia

Increased blood flow caused by enhanced tissue activity Metabolic (local) influence Active Hyperemia

Increased blood flow after removal of occlusion Metabolic (local) influence AND myogenic regulation Reduced intravascular pressure Decreased stretch Reactive Hyperemia

Metabolic vs Neuronal Control

Hormonal Influences  Under normal circumstances play a minor role in regulating blood flow  Following hormones are vasoconstrictors  NE and E (hemorrhagic shock)  ADH (hemorrhage)  Angiotensin II (hypertension?)

Summary  Myogenic regulation maintains a constant organ blood flow (at constant levels of tissue metabolism) with changes in perfusion pressure.  Changes in transmural pressure will change smooth muscle contraction  Autoregulation is maintaining constant organ blood flow which occurs via myogenic regulation  Intrinsic tone is the remaining constriction of the arterioles when all external influences are removed. This is what the other influences adjust  Neuronal tone is activation of the sympathetic fibers increasing vascular tone (i.e., vasoconstriction)  Local influence is the degree of smooth muscle contraction dependent upon the chemical composition of the interstitial fluid of the organ  Hormonal influence plays a minor role in regulating blood flow except under various physiological (e.g., exercise) and/or pathological stresses

Summary, cont  Active hyperemia is increased blood flow caused by enhanced tissue activity due to local (metabolic) influence  Reactive hyperemia is increased blood flow after removal of occlusion due to local (metabolic) influence and myogenic regulation  Blood flow to some organs such as heart and skeletal muscle has a higher responsiveness to metabolic than neuronal control. Blood flow to other organs such as GI tract, spleen, pancreas, and liver has a higher responsiveness to neuronal than metabolic control

Quiz Questions  Provide 3-5 multiple choice questions w/ feedback to each answer (correct or incorrect).

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