Regional Circulations

local mechanisms have two main functions

maintain blood flow at constant level

increase blood flow to tissue to meet enhanced metabolic needs

tone

contractile state of a resistance vessel is the vessel tone

active vasoconstriction

add SNS

active vasodilation

add adenosine or hormones/local factors

passive vasoconstriction

remove adenosine or active dilator influences

passive vasodilation

remove SNS

flow is maintained constant by altering

resistance as perfusion pressure changes

metabolic theory

if perfusion pressure increases, vasodilator metabolites are washed out of surrounding interstitial fluid and causes passive vasoconstriction and increase in resistance → flow returns to baseline

myogenic theory

increases in perfusion pressure causes increase in wall tension where vascular smooth muscle contracts in response to tension → resistance increases

intrinsic mechanisms to regulate BF

independent of neural and hormonal mechanisms

autoregulation

active functional hyperemia

reactive hyperemia

extrinsic mechanisms to regulate BF

neural control

endothelium-mediated control of vascular tone

hormonal control

autoregulation

metabolic theory and myogenic theory

active (functional) hyperemia

blood flow adjusted to meet metabolic demands of a tissue

as the rate of metabolism increases blood flow increases

metabolic vasodilators

K, CO2, local hypoxia, lactic acid

H+ ions, phosphate ions

prostaglandins

adenosine

adenine nucleotides

NO

adenosine

vasodilator metabolite

produced from ATP breakdown

released from cells when O2 supply/demand ratio is reduced (increased metabolism or hypoxia)

what is the most potent vasodilator in the body

NO

how does adenosine cause vasodilation

acts directly on vascular smooth muscle to increase cAMP concentration (A2 receptor (not alpha))

stimulates release of NO from vascular endothelial cells (A1 receptor (not alpha))

reactive hyperemia

increase in blood flow to tissue due to transient ischemia (inadequate blood flow due to something bad)

changes are due to local buildup of vasodilator metabolites during ischemic phase

longer time occluded = larger hyperactive response

neural control of vascular tone

sympathetic adrenergic fibers

sympathetic cholinergic fibers

parasympathetic cholinergic fibers

sympathetic adrenergic fibers

control vasc resistance in vasc beds

norepi innervates precapillary resistance

SNS vasoconstriction attenuated by local vasodilator metabolites or mediates

withdrawal of SNS → passive vasodilation

sympathetic cholinergic fibers

precapillary vessels in skin

acetylcholine

vasodilation mediated via M3 receptors on vascular endothelial cells and NO

parasympathetic cholinergic fibers

vasodilator fibers to small vascular beds: cerebral and coronary

do not directly affect TPR

endothelium mediated control of vascular tone

vasoactive substances bind directly to receptors on smooth muscle or to receptors on endothelial cells

vasodilating substances

NO

prostacyclin

endothelium deriving hyperpolarizing factor

bradykinin

ADP

vasoconstricting substances

endothelin

angiotensin II

thrombin

nitric oxide

gas released from endothelial cells → increase in cGMP pKG → vasodilation

endothelium derived hyperpolarizing factor (EDHF)

hyperpolarizes vascular smooth muscle → relaxes

unknown factor may be K+

prostacyclin (PGI2)

released by same cause of NO release

stimulates increase in intracellular cAMP → relaxation

inhibits platelet aggregation

endothelin

most active vasoconstrictor

mediated via ETa receptors, released in response to stretch of vessels and thrombin to constrict in response

autocoids

vasoactive molecules present in cells or formed from cell constituents

prostaglandins

kinins

histamine

prostaglandins

acts directly on vascular smooth muscle → vasoconstriction (PGH2 receptor)

arachidonic acid derivative

thromboxane produced by aggregating platelets

kinins

bradykinin and kallidin

arteriole vasodilator response mediated by endothelial NO via B2 receptor

increase venule permeability → cause capillary filtration

histamine

relaxes arterioles and precapillary sphincters and increases capillary permeability

vasodilator action mediated by H1 receptors on endothelial cells

stimulates NO release and by H2 receptors on vascular smooth muscle

• increases cAMP

vasoactive hormones

epinephrine

angiotensin II

vasopressin

ANP/BNP

epinephrine

most tissues → vasoconstriction

skeletal muscle → vasodilation due to higher B2 receptors for epinephrine

angiotensin II

potent vasoconstrictor acts directly on vascular smooth muscle AT1 receptors of resistance vessels

vasopressin (ADH)

potent vasoconstrictor acts directly on vascular smooth muscle of resistance vessels (V1 receptors)

ANP/BNP

vasodilator action results from stimulationg of guanylyl cyclase activity in vascular smooth muscle (ANP a/b receptors)

coronary circulation

high capillary density, large surface area short diffusion distances

almost complete oxygen extraction from blood

• blood flow must increase to increase O2 oxygen delivery to the heart: myocardial O2 delivery is FLOW LIMITED

regulation of coronary blood flow

autoregulation

active (functional) hyperemia

mediators/vasodilation

reactive hyperemia

primary determinant of coronary blood flow is

myocardial oxygen consumption (MVO2)

increase in MVO2 = increase in O2 demand = increase in coronary blood flow

heart regulates it’s own supply

major mediators of vasodilation for coronary blood flow regulation

adenosine

nitric oxide

adenosine and coronary blood flow

increase NO release and cAMP levels to relax coronary resistance vessels

nitric oxide and coronary blood flow

release from adenosine stimulation

reactive hyperemia and regulation of coronary blood flow

magnitude and duration of extra flow dependent on duration of the occlusion

sympathetic stimulation of neural regulation of coronary blood flow (functional sympatholysis)

increases coronary blood flow due to increase in production of metabolic vasodilators with increased O2 consumption (increased HR and contractility)

parasympathetic stimulation of neural regulation of coronary blood flow

parasympathetic stimulation of heart may be reduced coronary blood flow resulting from decreased HR and oxygen consumption

physical factors affecting coronary blood flow

coronary vessels are subject to systolic compressive forces within the myocardium

left coronary flow is inversely dependent on LV pressure (low LV pressure = high coronary flow)

right coronary flow is directly dependent on aortic pressure

skeletal muscle circulation capillary amount

as muscle cell size increases, number of capillaries decreases but typically 1:1 ratio of muscle fiber to capillary

neuralhumoral control on skeletal muscle blood flow

vasodilation at rest is passive due to withdrawal of SNS

norepi causes vasoconstriction at a1

adrenal medulla releases epi: less epi in B2 = vasodilation, more epi → vasoconstriction a1 a2

vasopressin and angiotensin II constrict

metabolism effect on skeletal muscle blood flow

with increased activity therre is increased vasodilator metabolites

functional sympatholysis - increased SNS with vasodilator metabolites increased as well

major mediators of vasodilation in skeletal muscle blood flow

increased potassium → Na/K ATPase → hyperpolarizes membrane

adenosine

NO

mechanical factors of regulating skeletal muscle blood flow

skeletal muscle pump

vessels are compressed during contraction phase → blood flow becomes intermittent (during exercise like weightlifting sustained contraction)

baroreflexes increase vascular smooth muscle tone resulting in increased venous return to the heart when sensing decreased arterial pressure

role of skeletal muscle circulation in blood pressure control

TPR regulated by controlling muscle vascular resistance

resistance influenced by vasoconstrictor activity, metabolic vasodilators, regulation by reflex mechanisms

cutaneous circulation primary function

maintain constant body temperature by providing convective transport of heat to body surface for exchange with the environment

major role in BP control

two types of resistance vessels in the skin

arterioles

arterio venous anastomoses (bypass capillaries)

AVAs are abundant where

regions of skin with high surface to volume ratio like fingertips, palms, toes, soles, ears, nose lips

AVAs control

sympathetic vasoconstrictor innervation has exclusive control of tonic activity by shunting blood from capillary bed

little metabolic control - no autoregulation or reactive hyperemia

arterioles control of blood vessels

sympathetic vasoconstrictor innervation - little activity at normal core temperature

vasodilator innervation is prominent to sweat glands → bradykinin

arterioles exhibit autoregulation, reactive hyperemia and basal tone

conservation of heat and AVAs

SNS adrenergic activity increases causing vasoconstriction and reducing heat transfer to the environment (a2 norepi)

dissipation of heat and AVAs

SNS adrenergic activity reduced and SNS cholinergic activity enhanced causing vasodilation and enhanced heat transfer to environment (ie sweating)

cold induced vasodilation

extreme cold = smooth muscle becomes paralyzed and vasodilation occurs

physical compression (sitting)

ischemia → accumulation of metabolites → stimulates nociceptors → pain → shift weight → reactive hyperemia

hormones role in cutaneous blood flow

epinephrine → constriction

angiotensin II → constriction

vasopressin → constriction

role of cutaneous circulation in blood pressure control

MAP = CO x TPR

hypotension → increase SNS → AVA, arteriole and venous constriction → increase TPR and mobilization of blood

cerebral blood flow at rest vs during exercise

should remain the same

needs large and steady arterial supply of O2

collateral channels exist to supply high blood flow and metabolism

cerebral blood volume must be tightly controlled to prevent elevation of intracranial pressure

blood brain barrier

tight junctions between endothelial cells prevent circulating vasoactive substances from affecting cerebral blood flow

driving pressure for cerebral blood flow

CBF = MAP - ICP

increase in MAP = decrease in ICP

sympathetic nervous system control on cerebral blood flow

no tonic influence

increase SNS may prevent hyperperfusion during acute increase of MAP

parasympathetic nervous system control on cerebral blood flow

stimulation causes vasodilation (ACh stimulates NO release)

innervation of larger vessels

unknown importance

nitrergic nerves on cerebral blood flow

parenchymal nitrergic neuronsin increase nerve activity = increase NO release = vasodilation

mediates local increase in flow during increase in neural activity

hypercapnia blood gas control on cerebral blood flow

arterial PCO2

• hypercapnia increased PCO2 → dilation → increase blood flow

• CO2 diffuses from blood into brain ECF to make bicarbonate + H

• increase H ions = vasodilation, blocks Ca entry into vascular smooth muscle and hyperpolarizes membrane

hypocapnia blood gas control on cerebral blood flow

decreased PCO2 → constriction → decreased blood flow

what has little effect on cerebral blood flow

arterial acidosis since H does not cross BBB

metabolic control of cerebral blood flow

potassium: vasodilation through hyperpolarization

adenosine: vasodilation

NO: vasodilates

CNS response to ischemia

if CPP falls below autoregulatory range the medullary vasomotor center becomes ischemic

SNS responds with vasoconstrictor activity to increase TPR, MAP, and increase CPP and cerebral blood flow

cushing’s reflex

space occupying lesion will increase ICP

forces brainstem down into foramen magnum

ischemia

increase in SNS drives vasoconstriction → increase in TPR, MAP, CPP, cerebral blood flow

baroreceptor mediated bradycardia