Local Control of the Vasculature Flashcards
Recall that smooth muscle contraction/vasoconstriction is triggered by
- Increase cytoplasmic Ca2+
- Ca2+ binds calmodulin
- Ca-calmodulin activates myosin light chain kinase
- crossbridge cycling
Mechanisms of vasorelaxation
cAMP, cGMP, or activation of K+ channels block the increase in cytoplasmic Ca2+ that drives vasoconstriction
Ex) NO promotes cGMP
Ex) prostacyclin (PGI2) promotes cAMP;
Ex) Drop in pH outside the cell activates K+ channels
How does extracellular potassium cause hyperpolarization AND vasodilation?
(smooth muscle-specific)
- Small increases in extracellular K+ activates the Na/K-ATPase –> take in K+, kick out Na+
- Na+ efflux activates Na/Ca exchanger reduces cytoplasmic Ca+ –> take in Na+, kick out Ca++
- Hyperpolarization & vasodilation
Extrinsic Regulation(brains shunts blood flow to specific vascular bed) is achieved by what 2 mechanisms?
Hormonal : release vasodilators & vasoconstrictors into the circulation by peripheral organs
Neural (ANS): sympathetic vs sympathetic
Vasoactive intestinal peptide (VIP)
&
Atrial natriuretic peptide (ANP) are
Vasodilators
Renin-angiotensin system
Vasoprsesin (ADH)
Epinephrine
are
Vasconstrictors
Sympathetic signaling is tonically active and promotes increased blood pressure via…
It’s mediated through ___ signaling
- increased CO
- Mobilization of blood reserves
- General vasoconstriction
Adrenergic signaling
Parasympathetic signaling promotes decreased cardiac output how?
- Cholinergic signaling
- A few resistance vessels are innervated by Ach promoting vasodilation
Sympathetic activity dominates in the skin.
The basal tone for cutaneous circulation is extremely ___
Changes in blood flow to the skin via vasoconstriction are used to regulate body temp
Basal tone for cutaneous circulation extremely low.
Adrenergic receptors are located in multiple organs and are activated by binding ____.
Differentiate between the different adrenergic receptors (esp the first 3)
Catecholamines
Vasodilation & vasoconstriction via adrenergic signaling in arterioles.
- Norepinephrine from sympathetic nerve terminals –> a1-adrenergic receptors –> VASOCONSTRICTION
- Epinephrine from adrenal medulla –> B2-adrenergic receptors –> VASODILATION in skeletal muscle and lungs
Catecholamines are the ligands for adrenergic receptors released in response to ____.
Sympathetic activity of the ANS.
Norepinephrine vs Epinephrine - where are they released from; what do they activate and where?
-
Norepinephrine: released from sympathetic nerve terminals
- Activates adrenergic receptors –> vasoconstriction of arterioles & veins
-
Epinephrine released by the adrenal gland & circulates
- Activates B1 (heart) and B2 (lungs & arteries)
- B2 expression primarily in skeletal muscle
- At high conc, it also activates a-adrenergic receptors in arteries
- Activates B1 (heart) and B2 (lungs & arteries)
Cholinergic (Muscarinic) Receptors - what do they facilitate and what’s the main agonist?
Facilitates parasympathetic signaling –> vasoconstriction on smooth muscle
Main agonist: acetylcholine
M2 vs M3 muscarinic receptor
M2: decreases cardiac output; in the heart
M3: vasodilation in the endothelium of resistance vessels that receive parasympathetic fibers (salivary glands, cerebral, and GI glands)
Dopamine is released by ___. How does it work?
- Released by tubule cells of kidney
- Its effect is concentration-dependent: it has the greatest affinity for the D1 receptor, but at higher conc will start activating B1, then a1 receptors.
- Stimulation of
- D1 receptors induces vasodilation & diuresis
- B1 receptors increases cardiac output
- a1 receptors promotes vasoconstriction
Sympathetic activity activates what receptors?
Parasympathetic activity activates what receptors?
- Sympathetic
- B1 -> increase CO
- a1 -> vasoconstriction shunting blood away from non-metabolically active tissue
- B2 -> vasodilation in skeletal muscle
- Paraympathetic
- M2 -> decrease CO
- M3 -> vasodilation
Myogenic response
Bp increases are matched with increases in smooth muscle contraction –> blood flow is maintained constant
Independent of the endothelium; protects capillary beds from high bp
___ circulation exhibits an excellent myogenic response between 60-160 mmHg. Thus, fluctuations in bp have a minimal effect on the cerebral blood flow
cerebral
Between 60-160mmHg, blood flow is maintained constant by progressively constricting the arteriole. Lower than that, blood flow is lost as the artery begins to collapse; higher than that, the arterial pressure begins to exceed the ability of the myogenic response to constrict and blood increases
3 intrinsic regulation mechanisms (vasomotion in response to the needs of local tissue)
metabolic factors
endothelium-dependent regulation
myogenic response
As your tissue performs metabolism and you need more O2, what happens (metabolic-dependent intrinsic regulation)?
- Adenosine increases->A2 receptor -> cAMP production -> vasodilation
-
H+, CO2, K+ increases -> vasodilation
- Drop in pH opens KATP channels -> K+ blocks Ca2+ entry and contractio n
- CO2 accompanies the drop in pH
___ activity is the main regulator of vascular tone in resting skeletal muscles. The vascular bed exhibits a __ basal tone, reducing blood flow.
Symathetic
reducing blood flow
What happens to active and inactive skeletal muscle during exercise?
Shunt blood only to active muscles
- Increased sympathetic activity reduces blood flow to inactive muscles
- a1 response dominates
- Release of metabolic factors in active muscle drive vasodilation of those arterioles supplying blood to active muscles
Compare the basal tone and vasoconstriction/dilation response of vessels in skeletal muscle vs skin
-
Skin
- Low basal tone
- Greater max vasconstrction
- No vasodilation
-
Muscle
- High basal tone restricts blood flow at rest
- Vasoconstriction and vasodilation responses to changes in sympathetic activity
- In exercise, metabolic effects overcome the vasoconstriction in active muscles –> vasodilation
Hyperemia
Blocked blood flow –> vasodilating metabolites accumulate in the tissue so that when flow is restored, the buildup promotes excess flow for a period until the metabolites wash out.
Endothelium-dependent regulation
Endothelium releases vasoactive compounds in response to circulating factors or shear stress (produced by flow)
- Vasodilation - Prostacyclin, NO
- Vasoconsriction - Endothelin
Prostacyclin (PGI2) and nitric oxide are both vasodilators. What are they released in response to? What do they do?
-
PGI2
- response to shear stress
- promotes increased cAMP in smooth muscle
-
NO
- response to ATP, Ach, bradykinin, serotonin, substance P, histamine, shear stress
- diffuses freely into smooth muscle
- increases in cGMP
Endothelin
Vasoconstrictor released by endothelial cells in response to turbulent flow and hormonal factors (e.g. angiotensin, ADH)
Note: Endothelin release does not continue to increase if flow becomes more turbulent; it’s released in response to the presence of turbulence
ACh stimulates conversion of L-arginine to ___, which diffuses into vascular smooth muscle and stimulates ___ to increase __ levels.
ACh stimulates conversion of L-arginine to NO, which diffuses into vascular smooth muscle and stimulates guanylyl cyclase to increase cGMP levels.
–> vasodilation
Nitroprusside (NP) acts directly on vascular smooth muscle to increase ___ levels in an endothelial cell indepenent manner
cGMP –> vasodilation
Cyclooxygenase and prostacyclin synthase converts arachidonic acid to prostacyclin (PGI2). What impact will this have?
Vasodilation
Compare and contrast instrinsic vs extrinsic mechansisms
