Local and Humoral Control - Student.pdf

LOCAL AND HUMORAL CONTROL OF TISSUE BLOOD FLOW NRAN 80413 SPRING 2024 RON ANDERSON, M.D. 1 MECHANISMS Acute control – Occurring within seconds to minutes via: Local mechanisms Neurohumoral mechanisms Long-term control – Over days to months Due to change in size or number of blood vessels 2 BASELINE...

LOCAL AND HUMORAL CONTROL OF TISSUE BLOOD FLOW NRAN 80413 SPRING 2024 RON ANDERSON, M.D. 1 MECHANISMS Acute control – Occurring within seconds to minutes via: Local mechanisms Neurohumoral mechanisms Long-term control – Over days to months Due to change in size or number of blood vessels 2 BASELINE TONE Partial constriction of the resistance vessels which allows both vasodilation and further vasoconstriction The walls of the resistance vessels are composed primarily of smooth muscle Variation of smooth muscle contraction then allows: Preferential distribution of blood flow throughout the body Control of arterial and venous tone Total peripheral resistance 3 VARIATION IN TISSUE BLOOD FLOW GUYTON 4 5 SMOOTH vs SKELETAL MUSCLE Smooth muscle contraction: – Develops very slowly – Develops high forces – Maintains contraction for long periods 6 MECHANISMS OF CONTRACTION Electromechanical coupling – Increased myoplasmic Ca++ via voltage gated calcium channels Pharmacomechanical coupling – 10 mechanism – Via receptor mediated calcium channels – Occurs in the absence of electrical excitation Relaxation occurs as Ca++ is pumped back into the sarcoplasmic reticulum or out of the cell 7 SMOOTH MUSCLE CONTRACTION MOSBY 8 SUBSTANCES INVOLVED IN PHARMACOMECHANICAL COUPLING Catecholamines Histamine Acetylcholine Serotonin Angiotensin Adenosine Nitric Oxide CO2 Potassium Prostaglandins 9 TWO THEORIES OF LOCAL BLOOD FLOW REGULATION Vasodilator Theory Oxygen Lack Theory 10 LOCAL BLOOD FLOW REGULATION VASODILATOR THEORY OXYGEN LACK THEORY GUYTON 11 VASODILATOR THEORY Vasodilator substances produced and released due to an increase in metabolism or a decrease in supply of oxygen or other nutrients Proposed vasodilator substances Adenosine CO2 Histamine K+ or H+ ions Nitric oxide Prostaglandins Combination of above 12 OXYGEN LACK THEORY In the absence of adequate oxygen (or some other nutrient), the smooth muscle is not able to maintain contraction. When it relaxes the blood vessel dilates allowing more blood (and oxygen) to be provided. Too much blood flow (or hyperoxygenation) would allow increased contraction of smooth muscle, thereby decreasing blood vessel diameter and returning blood flow to an acceptable level. 13 GUYTON ACUTE CONTROL OF LOCAL BLOOD FLOW Reactive Hyperemia – Following occlusion of blood supply to a tissue, upon release of the occlusion the blood flow may increase to several times the baseline value – Duration related to duration of occlusion Active Hyperemia – Increased blood flow in highly active tissue E.g. exercising skeletal muscle LEVY 14 AUTOREGULATION Maintenance of, or rapid return to, approximately normal blood flow following abrupt changes in arterial pressure Two Proposed Mechanisms Metabolic Theory – Similar to oxygen lack theory of local blood flow regulation – Excess oxygen or other nutrient causes increased smooth muscle contraction with subsequent decrease in blood flow Myogenic Theory 15 MYOGENIC THEORY OF AUTOREGULATION Increase or decrease in pressure initially increases or decreases flow, however the change in transmural pressure initiates contraction or relaxation of vascular smooth muscle Stretch-induced vascular depolarization allows rapid Ca++ entry with resulting in contraction Independent of neurohumoral influences Independent of intact endothelium Overridden by metabolic needs of the tissue 16 MYOGENIC MECHANISM OF AUTOREGULATION 17 LEVY UPSTREM REGULATION OF VASODILATION Locally mediated vasodilation affects only the small arteries and arterioles, not the larger upstream arteries. When vasodilation occurs downstream it increases flow through the larger arteries upstream. This increased flow places a shear stress on the vascular endothelium upstream which releases EDRF (primarily nitric oxide) with subsequent vasodilation of these vessels 18 UPSTREAM REGULATION OF VASODILATION 19 LEVY BASELINE VASCULAR TONE Baseline tone in blood vessels is independent of nervous system input Possibly due to: – Myogenic activity in response to stretch imposed by the blood pressure – High oxygen content of arterial blood – Presence of Ca++ – Some unknown plasma factor 20 NEUROHUMORAL CONTROL Substances are both centrally and locally produced and released Vasoconstrictors – Norepinephrine – Released form sympathetic nerve endings and from adrenal medulla – Epinephrine – Released form the adrenal medulla – Angiotensin II – Widespread constriction of small arterioles resulting in increased peripheral resistance – Vasopressin (ADH) – Released from posterior pituitary – Also functions to increase tubular reabsorption of water – Endothelin – Released from damaged endothelial cells to produce local vasoconstriction and reduce bleeding 21 NEUROHUMORAL CONTROL Vasodilators – Bradykinin – Enzyme kallikrein activated by multiple factors, acts on alpha2-globulin to release kallidin, which is converted to bradykinin – Produces arteriolar dilation and increased capillary permeability – Important factor in capillary leakage in inflammation and in regulation of skin blood flow – Histamine – Arteriolar dilator and increases capillary permeability following release from inflamed or damaged tissues 22 OTHER FACTORS AFFECTING VASCULAR SMOOTH MUSCLE CONTRACTILE STATE VASODILATION Increased K+ Increased Mg++ Increased H+ Acetate Citrate Increased CO2 (cerebral) VASOCONSTRICTION Increased Ca++ Decreased H+ Increased CO2 (systemically via sympathetic nervous system) 23 LONG-TERM REGULATION OF BLOOD FLOW Regulates blood flow fairly well between blood pressures of 50-250 mm Hg. Occurs over days to months Primarily achieved through change in vascularity of tissues. GUYTON 24 STIMULATION OF ANGIOGENESIS Inadequate oxygen Lack of other necessary nutrients Mediators of angiogenesis – Multiple substances identified which stimulate vascular growth Vascular endothelial growth factor (VEGF) Fibroblast growth factor Angiogenin Stimulation of angiogenesis dependent on maximum need rather than average need 25