Flashcards in regulation 3 Deck (29):
Sympathetic stimulation directly activates:
independent of membrane depolarization
Sympathetic stimulation mechanism
1. Sympathetic terminals release NE
2. NE activates aARs on VSMCs
3. aARs in VSMCs are coupled to Gq
3. Gq activation causes IP3 production.
4. IP3 increases cytosolic Ca2+
(by activating SR Ca2+ release via IP3 receptors)
Minor case in skeletal muscle:
Circulating epinephrine can activate b2ARs on VSMCs,
This causes vasodilation through cAMP/PKA inhibition of MLCK.
Baroreceptor reflex =
SHORT TERM and rapid negative feedback mechanism for sudden changes in blood pressure.
High pressure baroreceptors
1. in aortic arch and carotid sinus
2. respond to increases in arterial pressure by increasing firing rate
Stretch of arterial walls activates
mechanosensitive eNac Na+ channels on baroreceptor cell membranes.
Inward current causes depolarization, triggers APs in neurons
Carotid sinus baroreceptors project to the:
“cardiovascular control center” in the medulla via glossopharyngeal nerve.
Aortic arch baroreceptors project via the:
Low pressure baroreceptors
1. in atria and vena cavae,
2. mediate “Bainbridge Reflex” (increase HR in response to stretch).
CV control center Feedback response via
changes in autonomic regulation of the heart and vasculature
Classic Baroreceptor Reflex
1. Increase in pressure increase firing rate of baroreceptors.
2. CV control centers decrease sympathetic and increase parasympathetic output.
3. In heart this causes decreases heart rate and inotropy.
4. In vasculature, decreased sympathetic tone causes vasodilation
Intrinsic control of the vasculature
1. Vasoactive metabolites
2. Myogenic response
3. Nitric Oxide
What is the primary mechanism to match blood flow in the capillaries to metabolic demand?
Vasoactive metabolites produced by metabolically active tissue =
local feedback control of blood flow.
Vasoactive metabolites will result in
1. decreased PO2
2. increased PCO2 (decreased pH), partially due to lactic acid
3. increased extracellular K+
4. increased adenosine
How do vasoactive metabolites increase adenosine?
As a byproduct of ATP hydrolysis:
binds to A2 purinergic receptors on VSMCs. A2 receptors are GPCRs coupled to Gs = increased cAMP, vasodilation via inhibition of MLCK
Stretch-activated ion channels of Trp family in VSMC membrane.
1. non-selective cation channels, many isoforms
2. inward current depolarizes cell, also direct Ca2+ entry = vasoconstriction, reduces flow
Basal NO release helps set
resting vascular tone
Nitric oxide is a major physiological mechanism for _____.
NO action in VSMCs
1. NO diffuses across membranes to
2. VSMCs, where it activates guanylate cyclase to produce cGMP
3. cGMP activates PKG
4. PKG reduces intracellular Ca2+ via activation of SERCA, and inhibition of L-type Ca2+ channels
5. Decreased Ca2+ causes vasodilation via reduced MLCK activity
endothelin is a
potent vasoconstrictor, produced by vascular endothelium
endothelin converting enzyme (ECE)
rate limiting step
endothelin is stimulated by
angiotensin, ADH, thrombin
endothelin is inhibited by
NO and ANP
endothelin is released form
vascular endothelium binds to ET receptors on VSMC (GPCRs coupled to Gq).
endothelin negative feedback
via ET receptors on endothelial cells = NO production.
similar to α adrenergic response (vasoconstriction via IP3 and increased Ca2+) but different time course.