Endothelial vasodil/vasoconst Flashcards
Major mechanisms controlling peripheral vasc resistance
- Vasoconstrictor receptors
o incr [intra¢ Ca2+] => promote vasoconstriction
o Respond to agonists from neurogenic, humoral, endothelial fct
A1 adrenergic R => NE
Ang II => vasoconstrictor + incr NE release
ET-1 => released from damaged endothelium - Cyclic nucleotide vasodilatory system
o cAMP/cGMP: inhibit vasoconstriction by inhibiting myosin light chain kinase
B adrenergic stimulation=> incr cAMP
NO => incr cGMP
Principal determinant of vasomotor tone (cellular pathways)
depends on final common pathway = cytosolic Ca2+ availability for muscle contraction
* Agonist => G-prot ¢ membrane R => phospholipase C =>
o Diacylglycerol (DG) => Ca2+ dependant prot kinase => Na/H exchanger
o Inositol triphosphate (IP3) => direct cytosolic Ca2+ from SR => available for myosin
Def of endothelial signaling
Small molecule locally produced in arterioles
Local vasodilators
NO
Prostacyclin
ET derived hyperpol factor
Adenosine
Local vasoconstrictors
Endothelin
Factors inhibiting vasodilators activity
Hypoxia
Thrombin
O2-derived free radicals
o Also incr ET1 release
Effect of NO release
released from endothelial ¢ lining blood vessels
Reason why exercise induce vasodilation => vasodilatory local messenger
NO release
* psymp stimulation
* Shear stress 2nd to incr blood flow in normal endothelium
incr cGMP induced vasodilation
Effect of adenosine
Act on adenosine R on vascular SM¢
Inhibit release of NE
Effect of endothelin
release stimulated
Shear stress if damaged endothelium
* Act on ETA R => vasoconstriction
Low doses/physiologic = vasodilatory via ETB => NO release
CNS control of endothelium
Stimulation via
o Ao baro/chemo R => vagus nerve => medulla
ChemoR less important for BP regulation => acidosis or hypercapnia => incr BP
o Carotid sinuses & bodies => glossopharyngeal nerve => medulla
o Cardiopulmonary R
o Stretch R in A, V, PA
Effect of decr BP on CNS
activation of symp + suppression of psymp => incr HR, contractility, arterial + venous vasoconstriction, renin release, Na retention
Effect of incr BP on CNS
carotid + Ao baroR => nucleus solitarius in brainstem => vagal nucleus => vagal stimulation => symp inhibition => decr HR and inotropy => decr CO => decr BP
o Expected reflex bradycardia in acute incr BP
o Carotid sinus massage can also initiate response
What are the neurotransmitter of symp system
Norepinephrine (NE): stimulates
* Myocardial B adrenergic R => incr HR
o HR decr after initial transient incr because pressure sensitive control mechanism
* Vascular A adrenergic R => vasoconst
* Formed in variscosities of terminal nerves
o Dopa + dopamine => amino acid tyrosine
Epinephrine: stimulates
* Myocardial B adrenergic R => incr HR
* Vascular B adrenergic R => vasodilation
o Overall effect: incr systolic BP and decr diastolic BP = stable mean BP
o = incr CO + incr limb blood flow
Type of R of symp system
A adrenergic R
* A1 = vascular SM¢ => vasoconstriction
o Postsynaptic receptors (sarcolemma)
* A2 = adrenergic nerve terminal => inhibit NE release
o Feedback inhibition of its own release
o Presynaptic receptors
B adrenergic R
* B1 = heart => incr contractility + HR
* B2 = sinus node => incr HR
= vascular SM¢ => vasodilation
* B3 = decr contractility
A2 = adrenergic nerve terminal => inhibit NE release
Signaling of symp system once R activated
NE bind to B adrenergic R => stimulatory G protein => activates adenylate cyclase => conversion of ATP => cAMP
* incr opening of Ca2+ channel => promotes Ca2+ entry
* incr release of Ca2+ by SR => incr [Ca2+] => incr contractility
In sinus node: cAMP icnr rate of spontaneous pacemaking