Local Control of Blood Flow Metabolic hypothesis: Blood flow is governed by the metabolic activity of the tissue. Any intervention that reduces O 2 supply gives rise to the formation of vasodilator metabolites. Myogenic hypothesis: The vascular smooth muscle contracts in response to stretch
Metabolic hypothesis The metabolic hypothesis suggests that the tissue releases a vasodilator; The potential mediators of this vasodilation are: Adenosine Prostaglandins Lactate
Local modulators of blood flow Nitric Oxide is a potent vasodilator that relaxes vascular smooth muscle and is released when flow is increased to a vascular bed. Endothelin is a family of peptides that are potent vasoconstrictors.
What causes exercise hyperemia? A collection of examples that do not alter exercise hyperemia ? –Substances released by active muscle Nitric oxide, ATP, Prostaglandins, Adenosine –Mechanical pumping of muscle –Nerves Sympathetic withdrawal, Sympathetic vasodilator fibers, Acetylcholine from muscle nerve fibers Maybe a combination of factors synergize. Maybe there is (are) some unknown factor(s). Note: Some of these substances are important during ischemia (e.g. adenosine) or when oxygen demand and delivery are briefly mismatched
Scale bar = 100 m. J. Of Neuroscience Methods 184:124-128,2009 Muscle arteries are, but capillaries and veins are not, innervated in C57BL6 mice Mesenteric vein Mesenteric Artery Femoral artery Gracilis Feed artery
Working muscles compete for blood flow Med. Sci. Sports Exer. 38:797,2006
Brain Blood Flow is very sensitive to PaCO 2 Arterial PCO 2 is a cerebral vasodilator Mohrman and Heller et al X X
Contrary to popular belief cerebral blood flow increases during exercise The magnitude of the increase is dependent on the method used to assess blood flow –Xenon gas washout –Doppler flow The flow response is dependent on exercise intensity
Exercise & Sport Sciences Reviews. 37(3):123-129, July 2009.
August Krogh (Univ. of Copenhagen) was awarded the Nobel Prize for Medicine on October 28, 1920 for discovering how increased O 2 uptake by tissue is regulated via the recruitment of capillaries Basic premise: Diffusion depends on the concentration gradient and diffusion distance. To increase the rate of O 2 diffusion (e.g. exercise) you either increase the concentration gradient or decrease diffusion distance
Krogh’s model is incomplete? Capillaries are not straight and they are stretched when sarcomere length is increased Capillaries are not recruited they are always open Capillary hematocrit increases during exercise (10-15% to 30-40%) PO 2 is very low in mitochondria at rest Oxygen can diffuse from arterioles Flow can be countercurrent
Dynamics of Muscle Microcirculatory Oxygen Exchange. POOLE, DAVID; BEHNKE, BRAD; PADILLA, DANIELLE Medicine & Science in Sports & Exercise. 37(9):1559-1566, September 2005. Mouse Soleus Muscle Erythrocyte Mitochondria 0.5 m
Tissue oxygen is very low Dynamics of Muscle Microcirculatory Oxygen Exchange. POOLE, DAVID; BEHNKE, BRAD; PADILLA, DANIELLE Medicine & Science in Sports & Exercise. 37(9):1559-1566, September 2005.
Flow increases very rapidly with the first contraction POOLE, DAVID; BEHNKE, BRAD; PADILLA, DANIELLE Medicine & Science in Sports & Exercise. 37(9):1559-1566, September 2005.
Diffusion is determined by capillary PO 2 and diffusive capacity
Spinotrapesius muscle and microvascular PO 2 POOLE, DAVID; BEHNKE, BRAD; PADILLA, DANIELLE Medicine & Science in Sports & Exercise. 37(9):1559-1566, September 2005.
Low flow states limit dynamic vascular response to exercise CHF=congestive heart failure
Microvas. Res 55:249-259,1998. Counter current flow
Clark, M. G. Am J Physiol Endocrinol Metab 295: E732-E750 2008; Proposed schematic blood flow patterns in muscle in vivo under basal conditions and following a physiological rise in plasma insulin
As O 2 delivery decreases, the speed with which the tissue can respond to O 2 demand slows ( ↑τ ) Medicine & Science in Sports & Exercise. 40(3):462-474, March 2008. Delivery dependent VO 2 kinetics Muscle metabolism dependent VO 2 kinetics
Muscles are not the same Slow-twitch oxidative Fast-twitch glycolytic Fast-twitch oxidative e.g. slow-twitch vs. white fast twitch fibers have increased capillarization, arteriolar density, oxidative capacity, and endothelium-dependent dilation
Microvascular PO2 following 1Hz stimulation Medicine & Science in Sports & Exercise. 40(3):462-474, March 2008. Soleus White Gastroc. Mixed Gastroc.
They are recruited differently in response to gradual increases in exercise intensity First recruit slow oxidative then fast glycolytic
Duncker, D. J. et al. Physiol. Rev. 88: 1009-1086 2008; Hemodynamic responses to treadmill exercise in dogs
Duncker, D. J. et al. Physiol. Rev. 88: 1009-1086 2008; Overview of the effect of exercise on myocardial oxygen balance
Duncker, D. J. et al. Physiol. Rev. 88: 1009-1086 2008; Schematic drawing of a coronary arteriole and the various influences that determine coronary vasomotor tone and diameter
Nitric oxide (NO) release throughout the exercise training cycle. The improvement in NO-related vasodilation is observed in short- to medium-term exercise training, whereas prolonged exercise is associated with arterial remodelling through an increase in vessel diameter. Furthermore, strenuous exercise may promote endothelium release of reactive oxygen species (ROS) as an additive source of oxidative stressors (modified from Green et al.). cGMP = cyclic guanosine monophosphate; eNOS = endothelial nitric oxide synthase; GC = guanylate cyclase; GTP = guanosine triphosphate. Sports Medicine. 39(10):797-812, October 1, 2009.