Vasoactive (General) Flashcards
Why is it important to maintain proper blood pressure
Sympathetic System ensures all organs get proper blood flow
Helps regulate body temperature
Cardiac Preload
Initial stretching that occurs during ventricular filling
Higher Preload = Higher Afterload
Cardiac Afterload
Pressure that heart has to pump against and overcome
Greater Pressure = Greater Load, Heart has to pump harder
Capacitance Vessels
Venous System:
- Stores blood
- Most blood is stored in venous system
- Stored blood can be recruited when needed
Resistance Vessels
Arterial System
- Lots of control
- Provides resistance to blood flow
Vascular Tone
- What parts of vascular system have muscles
- What kind of muscle is this?
- What is the function of these muscles?
Wall of arteries, arterioles, venules, veins all contain smooth muscle
- Less smooth muscles in veins
Controls vasodilation/vasoconstriction
What controls Vascular Tone
Endothelium
Circulating Hormone
Sympathetic Nerve
How is Vascular Tone controlled
Ca2+ regulates vascular smooth muscle cells
- Vascular SM contracts when Ca2+ rises
–> Vasoconstriction
- Vascular SM relax when Ca2+ decreases
–> Vasodilation
Process of Muscle Contraction
- Ca2+ rises, forms complex if Calmodulin
- Complex activates Myosin Light Chain Kinase (MLCK)
- MLCK phosphorylates myosin
- Myosin can now crossbridge with actin
- Initiates contraction
Process of Muscle Relaxation
Myosin Light Chain Phosphatase (MLCP) dephosphorylates MLC leading to relaxation
–> Inhibition of MLCP maintains contraction
Methods Agents use to Cause Contraction
Increase Ca2+:
- Release intracellular Ca2+ via IP3
- Depolarizing membrane and opening voltage-gated Ca2+ channels
–> Allow Ca2+ entry intro cell
MLCK/MLCP Activity:
- Increase MLCK activity
- Decrease MLCP activity
Methods Agents use to Cause Relaxation
Decrease Ca2+:
- Hyperpolarize membrane (Open K+ Channels)
- Inhibit Ca2+ entry by blocking VGCC
cGMP/cAMP rise –> Vascular Smooth Muscle Relaxation:
- Increase Intracellular cAMP
–> Activates MLCP & promote Ca2+ efflux
- Increase intracellular cGMP
–> Activates MLCP & opposes agonist induced Ca2+ increase
Vascular Tone (Endothelium)
Produces Vasodilators and Vasoconstrictors
- Also important for platelet regulation
Vascular Tone (Endothelium)
- Vasodilation
Major Vasodilators Produced by Endothelial Cells
Nitric Oxide (EDRF = Endothelial Relief Factor)
Prostanoids (PGI2)
Endothelial-Derived Hyperpolarizing Factor (EDHF)
–> Most likely Ca2+ activated K+ Channels that cause hyperpolarization of Endothelium which spreads to smooth muscles
C-Natriuretic Peptide (CNP)
–> Increase cGMP
Vascular Tone (Endothelium)
- Vasoconstrictor
Major Vasoconstrictors Produced by Endothelial Cells
Endothelin
Thromboxane A2 (Platelets)
Angiotensin II
Endotheline (ET)
- Produced by?
- Hormone or Local Mediator
Endothelial Cells
Acts as a local mediator
Endotheline (ET)
- Mechanism of Action
- Effect
Binds ET(A) Receptors expressed by Vascular Smooth Muscle Cells
Causes vasoconstriction by IP3-mediated Ca2+ release
Vascular Tone (Circulating Hormones)
- What are the different methods hormones control vascular tone?
1 Renin-Angiotensin System (RAS)
- Antidiuretic Hormone (ADH/Vasopressin)
- Bradykinin
Renin-Angiotensin System (RAS)
- Overall Effect
Vasoconstriction
- Aldosterone stimulates salt/water reabsorption by kidney
Renin-Angiotensin System (RAS)
- Entire Process
- Renin is secreted by Kidney
- Renin cleaves Angiotensinogen into Angiotensin I
- Angiotensin-Converting Enzyme cleaves Angiotensin I into Angiotensin II
- Ang II Binds AT1 receptors on SMC resulting in vasoconstriction
Antidiuretic Hormone (ADH/Vasopressin)
- Released by?
- Effect
Secreted by posterior pituitary
Causes vasoconstriction by:
- Binding V1 Receptors on Smooth Muscle Cells
- Water retention
Bradykinin
- Released by
- Effect
Generated from Kininogen by Kallikrein
Mediates vasodilation by endothelial NO generation
What does ACE do
Cleaves Angiotensin I to Angiotensin II
Cleaves and inactivates vasodilator bradykinin
Vascular Tone (Sympathetic Nerves)
- Regulates what?
Regulates arterial, arteriole, venous, vein diameter
Vascular Tone (Sympathetic Nerves)
- Stimulation
Sympathetic Nerve stimulation releases norepinephrine (NE)
- Effects are Vascular System Dependent
Vascular Tone (Sympathetic Nerves)
- NE acts on Alpha-1 Smooth Muscle Cells
Induces Vasoconstriction
- Ex. BP regulating resistance arteries
Vascular Tone (Sympathetic Nerves)
- NE acts on Beta-2 Endothelial Cells
Induces Vasodilation
- Ex. Blood vessels of skeletal muscles
