Pressure and Flow Control Flashcards
Primary source of nitric oxide
endothelium
Intrinsic Mechanism
Local control
Often does not affect systemic blood pressure; only affects local mechs
Autoregulation - tissues can control their own blood flow to meet their metabolic needs
Extrinsic Control
Autonomic NS and circulating hormones regulate BP
Essential driving force for blood flow and redistribution
Mechanisms involved in autoregulation (keeping flow constant)
- Myogenic - smooth muscle
- Metabolic
- Paracrine - substances released locally
How does flow stay constant
Changing resistance
MEtabolic Autoregulation
Matching flow with tissue metabolic activity
Metabolites = local vasodilation
Inc them, inc blood flow to wash out the metabolites
Then blood flow will decrease until metabolites accumulate again
Hyperemia
Increase in flow
- Active - dilation in response to inc metabolic activity (exercise)
- Reactive - increase in accumulation of vasodilator metabolites due to occlusion (happens every single beat - BP cuff)
Myogenic Autoregulation
Inc transmural pressure causes smooth muscle vasoconstriction
Activation of stretch will activate the stretch activated channels on the VSM
This induces depolarization and Ca influx
Decrease in transmural pressure would cause smooth muscle ____
dilation
Inc in arterial and transmural pressure —>
Stretch of smooth muscle –> contraction of the muscle –> arteriolar constriction –> dec in blood flow
Paracrine Mechanism - major dilators
Nitric Oxide
Prostacyclin
EDHF
Paracrine Mechanism - major constrictors
Angiotensin II
Thromboxane A2
Endothelium
Metabolic - dilate or constrict
Vasodilator
metabolites
Myogenic Control - dilate or constrict
Can do either
Depends on the stress
Inc pressure = constrict
Dec pressure = dilate
Paracrine - shear stress will cause
NO release from endothelium
Paracrine Dilators
Relax
- NO
- Prostacyclin
- EDHF
Paracrine Relaxer - NO
Ach stimulates NO release
NO is produced from reaction with L-Arg (amino acid) and NOS (nitric oxide synthase - synthesizes NO)
NO then uses cGMP to produce relaxation
Paracrine Relaxer - Prostacyclin
From arachadonic acid
Inc cAMP to cause relaxation
Paracrine Relaxer - EDHF
Endothelium derived hyperpolarized factor
Takes membrane potential further away from potential by allowing K to leave the cell and therefore relax
What happens prior to symptoms of cardiovascular disease
Endothelial dysfunction
Key underlying Mechanisms - Endothelial Dysfunction
- Arginase also competes for L arg (like NO)
if arg is elevated will produce less NO - Could have less L-Arg around - so less NO
- Missing BH4 - get superoxide - free radical - oxidative stress
- Elevation of Rho Kinase - leads to dec in NO by inhibiting myosn light chain phosphokinase and keeps myosin in contracted state
Risk factors for cardiovascular disease
Hypertension Hypercholesterolemia Diabetes Mellitus Aging Obesity Smoking Meopause
What do risk factors of cardiovascular disease all have in common?
They all lead to oxidative stress –> endothelial dysfunction and therefore cardiovascular dysfunction
Extrinsic Control
Neural/Hormonal
Sympathetic = NE and adrenergic receptors
Parasympathetic = Ach and cholinergic receptors
Extrinsic - Sympathetic
Alpha adrenergic receptors = dense in vasculature, more sparse in heart, cause VC
Bete adrenergic = dense in heart, more sparse in vasculature, cause inc in HR and contractility and VD in vasculature
Extrinsic - Parasympathetic
Ach –> cholinergic receptors (muscarinic and nicotinic)
Limited innervation of vasculature
Reduces HR
Extremely limited to erectile tissue
With exercise what happens to flow and why?
Inc blood flow
SNA will inc resistance
MAP =
CO x TPR
Short Term Regulation of BP
Baroreceptors - beat to beat regulation Baroreflex is a pressure-lowering mechanism - Detects change in pressure - goes to center in medulla - effector = SNS to change BP
Long Term Regulation of BP
Pressure/volume receptors in kidneys adjust RAA system (Renin angiotensin aldosterone)
High Pressure Receptors location
Aortic arch and carotid sinus
Low Pressure Receptros location
AKA Cardiopulmonary Receptors
All chambers of the heart and great veins
As filling, pressure goes down and stimulates an increase in vasoconstriction
Cardiovascular Control Center =
Medulla
Afferent fibers project to medulla; specifically nucleus tractus solitarius (NTS)
Nucleus Tractus Solitarius receives inputs from
Respiratory Centers
Higher CNS center (emotion)
Baroreflex stimulates
Inhibitory interneurons project from NTS to vasomotor area
Excitatory interneurons project from NTS to coinhibitory area - stimulates parasympathetic vagus nerve
Drop in arterial pressure - what comes to rescue?
Get up too fast
Baroreflex There is a dec in baroreflex activity Inc symp nerve activity inc HR, contractility, vascular resistance, vasoconstriction BP will go up back to set point
Inc in arterial pressure - then what
Inc baroreceptor activity
Vagus responds and dec HR and dec CO and pressure will go down
Sleeper effect when in choke hold
Small drop in pressure will elicit what kind of change
A huge change
Make card on beat to beat regulation
As you dec. pressure you are inc sympathetic activity
Sympathetic nerve activity happens primarily during diastole
If you inc sympathetic nerve activity what tissues/organs are impacted most
Skin muscle and kidney are affected the most
Brain and heart are not impacted because to keep things constant we dont want to take away from the brain and heart
What will win with competition for flow?
Heart and brain
Reduced slope of the barorector curve means
Reduced gain or sensitivity - means baroreflex opposition to changes in BP would be reduced
Gain is reduced with most CV pathologies
Baroreflex is ____ to defend a new set point
Reset
When we increase intensity of exercise, we are shifting the set point
How does the resetting occur?
Central Command
Exercise Pressor Reflex
Central Common control of resetting
Feed forward mechanism
Central Command = feedforward control
If inc. output from motor cortex, then inc CC, and this results in inc sympathetic nerve activity
Exercise Pressor Reflex - resetting
= mechanoreflex and metaboreflex
If inc in metabolites and/or contraction in active muscle, Inc in sympathetic nerve activity
Greater motor output will do what to setpoint
Reset it
As metabolites build up - will also reset it
Long Term BP Regulation
Juxtaglomerular Apparatus
3 Cell types of JG Apparatus
- Granular Cells - release renin
- Macula Densa Cells - senses filtered Na load
- Extraglomerular mesangial cells
Renin Angiotensin Aldosterone System
JGA –> releases renin –> (renin converts angiotensinogen to angiotensin I –> converting enzyme in lungs converts angiotensin I to angiotensin II –> causes constrictor effect that will inc pressure –> acts on adrenal cortex and stimulates production of aldosterone (Na conserving hormone)
Inc volume, so pressure will go back up
Stimulus of drop in pressure/volume
Dec renal arterial pressure –> inc renin secretion
Will also activate baroreceptor reflex –> inc in sympathetic nerve activity –> inc in renin secretion
When renin is elevated, then what
Will produce Angiotensin II –> Vasoconstriction –> Inc peripheral resistance = inc BP
WHat 3 mechanisms aid in ncreasing renin secretion
Inc renal sympathetic nerve activity
Decrease in Macula Densa NaCl load
Renal Baroreceptor
What leads to vasoconstriction
Exercise pressure reflex
Central Command
Baroreflex
Myogenic
What leads to vasodilation
Metabolic autoregulation
Nitric oxide
Muscle pump
- these win during exercise - they outweigh the VC mechanisms so VD will occur
