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Flashcards in Regulation of CV system Deck (28):

Stroke volume is regulated by what 3 things?

1. Inotropy (contractility) +
2. Preload +
3. Afterload -


what is the most prevalent category of drug target?



Describe PKA tetramer

2 Regulatory and 2 catalytic subunits.

Binding of 4 cAMP molecules causes dissociation

Free catalytic subunit can phosphorylate target proteins


What does phospho of PLB do?

Relieves inhibition of SERCA
Leads to faster Ca2+ reuptake into SR
--> may enhance the rate of cardiac myocyte relaxation.

(When phospholamban is phosphorylated by PKA its ability to inhibit (SERCA) is lost.)


Phospho of RyR?

Increase Ca2+ sensitivity so less is needed to evoke Ca2+ release


Phospho of DHPR?

Slows inactivation
Increases entry of trigger Ca2+
Increase Ca2+ induced Ca2+ release = increases inotropy


Phospho of troponin I?

Decreases Ca2+ sensitivity of troponin C
Allows faster dissociation of Ca2+ so faster filling = increased lusitropy



Sympathetic stimulation ___ HR
Parasympathetic stimulation ____ HR

Symp = increase
Parasymp = decrease


cAMP binding stimulates HCN channels, this does what to inward current and AP generation?

Increases inward current and increasing spontaneous AP generation


What is primary mechanism for parasympathetic control of HR? Secondary mechanisms?

Primary is activation of IKACh current via GIRK (inwardly rectifying K+) channels --> lets current in at (-) potentials
hyperpolarization-activated K+ channel responsible for resting potential in ventricular myocytes

Secondary are the binding to M2 muscarinic Ach receptors, ↓ing cAMP


Striated muscle contraction = ___ filament regulation



Do VSMCs have sarcomeres?

(myofilaments of SM, unlike skeletal and cardiac are not arranged in sarcomeres)

They also have no troponin!


Describe the molecular steps involved in Ca2+ regulation of vascular smooth muscle contraction.

What permits cross-bridge cycling in VSMC?

1. Contraction is triggered by mechanical, chemical, or electrical stimuli.
2. Ca2+ enters cytoplasm from SR and/or PM Ca2+ channels
3. Ca2+ binds calmodulin
4. Ca2+-Calmodulin binds to myosin light chain kinase (MLCK) to activate it
5. Activated MLCK phosphorylates the myosin head - permits cross bridge cycling
6. MLC dephosphorylated by myosin light chain phosphatase (MLCP); stops contraction
7. cAMP inhibits MLCK - causes VSMC relaxation

Phophorylation of myosin head


cAMP inhibits MLCK which does what for VSMC and Cardiac cells?

causes VSMC relaxation!!! This is different from contraction in cardiac cells (contraction).


Is baroreceptor reflex an intracellular signaling pathway?

No, baroreceptors are pressure sensitive neurons, that provide short term and rapid negative feedback mechanism for sudden changes in blood pressure.

They don't contract. They respond to stretch.


4 vasoactive metabolites

Primary mechanism to match blood flow to capillaries to metabolic demand

1. PO2
2. PCO2
3. Increased extracellular K+
4. Increased adenosine (by product of HPV analysis)


Myogenic response (autoregulation)

Independent of metabolism, maintains constant flow despite changes in pressure (ie postural changes)

When you stretch isolated blood vessel, it constricts


Myogenic response can be overcome by what?

the vasoactive metabolites


NO signaling
- what is it?
- what is it produced by?

Potent gaseous vasodilator with short half-life (10-60s) so has local effects

Produced by vascular endothelium


Decreased NO is associated with increased risk for what condition?



What is the NO synthase sensitive to?

Components of cigarette smoke such that NO production can be compromised by CV disease risk factors

ie smoke cigarettes, get atherosclerosis (b/c NOS doesn't work and you don't get enough NO)


NO action in VSMCs?

○ Humoral regulators activate GPCRs on endothelium that increase intracellular Ca levels.
○ Increase intracellular Ca activates NO synthetase.
○ Free NO diffuses into VSMCs and activates guanylate cyclase
○ cGMP is increased and activates PRG, which activates SERCA and inhibits the L-type Ca channel.
○ Resultant decreased Ca causes relaxation (vasodilation)



Potent peptide vasoconstrictor produced by vascular endothelium

Endothelin Converting Enzyme (ECE) is the rate-limiting converting enzyme

Binds to GPCR on VSMC which are Gq coupled receptors, produces IP3 and increases Ca within VSMC and leads to vasoconstriction


What is the primary system for long-term control of blood pressure?



ACE does what?
what is it used to treat?

Converts Angiotensin I to Angiotensin II which is a vasoconstrictor.

Used to treat hypertension and heart failure


How does Angiotensin II work?

Binds to GPCRs on VSMCs - Gq linked to induce systemic vasoconstriction

Also stimulates sympathetic activity and release aldosterone, endothelin, and ADH


What is the role of aldosterone?

Increase blood volume and BP by promoting Na and water reabsorption


What is the role of ADH

Increases water reabsorption in kidney = increases blood volume and BP

Can also bind to receptors in vasculature to cause vasoconstriction