USMLE Forums banner
1 - 18 of 18 Posts

·
Registered
Joined
·
1,357 Posts
Discussion Starter · #1 ·
In an protocol, iv administration of acetylcholine was found to decrease MAP and increase heart rate. These results can best be explained by:

A. Direct action of acetylcholine on muscarinic receptors at the sinoatrial node.
B. Direct action of acetylcholine on muscarinic receptors in the arterioles of the skeletal muscle.
C. Increased firing of carotid sinus baroreceptors.
D. Reflex activation of sympathetic nerves.
E. Reflex systemic vasodilation.
 

·
Registered
Joined
·
324 Posts
In an protocol, iv administration of acetylcholine was found to decrease MAP and increase heart rate. These results can best be explained by:

A. Direct action of acetylcholine on muscarinic receptors at the sinoatrial node.
B. Direct action of acetylcholine on muscarinic receptors in the arterioles of the skeletal muscle.
C. Increased firing of carotid sinus baroreceptors.
D. Reflex activation of sympathetic nerves.
E. Reflex systemic vasodilation.
It can be D..
Others dont seem to be right..

Although, Ach has sympathetic effect on cardiac, smooth muscles, and glands thru nicotinic receptors..
 

·
Registered
Joined
·
298 Posts
There are Muscarinic receptors located on blood vessels but normally there is no ACh in the blood because it is a Neurotransmitter.

If ACh is given IV, it stimulates M3 receptors (Gq pathway) leading to smooth muscle relaxation via release of NO by endothelial cells and thus vasodilation. This vasodilation then triggers a reflex increase in HR. (Vasodilation leads to decreased BP/stretch and thus less firing of carotid baroreceptors, which disinhibits sympathetic system --> Leads to increased sympathetic drive and thus increased HR)

So the answer should be D
 

·
Registered
Joined
·
40 Posts
There are Muscarinic receptors located on blood vessels but normally there is no ACh in the blood because it is a Neurotransmitter.

If ACh is given IV, it stimulates M3 receptors (Gq pathway) leading to smooth muscle relaxation via release of NO by endothelial cells and thus vasodilation. This vasodilation then triggers a reflex increase in HR. (Vasodilation leads to decreased BP/stretch and thus less firing of carotid baroreceptors, which disinhibits sympathetic system --> Leads to increased sympathetic drive and thus increased HR)

So the answer should be D
Wouldn't Gq mediated receptor activation cause vasoconstriction? Alpha-1 adrenergic receptors are Gq linked
 

·
Registered
Joined
·
298 Posts
Wouldn't Gq mediated receptor activation cause vasoconstriction? Alpha-1 adrenergic receptors are Gq linked
Theoretically yes, but M3 receptors on blood vessels somehow lead to release of NO leading to vasodilation. It might not work via Gq but M3 receptors are the ones involved.

I just had a Kaplan question that tested this concept. ACh IV leads to vasodilation via M3 stimulation and reflex tachycardia

I dont know if anyone even knows how M3 stimulation leads to NO release, I just settled on memorizing this fact.
 

·
Registered
Joined
·
1,357 Posts
Discussion Starter · #9 ·
correct answer

The correct answer is D) Reflex activation of sympathetic nerves.

"Acetylcholine dilates blood vessels, which lowers arterial pressure and causes a baroreceptor-mediated increase in heart rate brought about by sympathetic activation."

This qs. is from: Cardiovascular Physiology Concepts
 

·
Registered
Joined
·
27 Posts
How do you guys get D as the answer without considering B. The way the question is asked it seems to ask the mechanism of BOTH the decrease in MAP and the increase in HR. The only way that I can see this happening, with the protocol of IV Ach is a direct action on the M3 receptor--> dialation via NO release ----> reflex increase in HR.

With B the flow of reasoning is linear and forward (cause --> effect) and with D its the opposite (effect ---> cause).

How do you guys decide what the answer is between these 2?
 

·
Registered
Joined
·
1,357 Posts
Discussion Starter · #11 ·
How do you guys get D as the answer without considering B. The way the question is asked it seems to ask the mechanism of BOTH the decrease in MAP and the increase in HR. The only way that I can see this happening, with the protocol of IV Ach is a direct action on the M3 receptor--> dialation via NO release ----> reflex increase in HR.

With B the flow of reasoning is linear and forward (cause --> effect) and with D its the opposite (effect ---> cause).

How do you guys decide what the answer is between these 2?
I guess it's because the drug only explain the first part of the question (decrease in MAP), but what we really need to explain is why the frequency went up ... :rolleyes:
 

·
Registered
Joined
·
116 Posts
How do you guys get D as the answer without considering B. The way the question is asked it seems to ask the mechanism of BOTH the decrease in MAP and the increase in HR. The only way that I can see this happening, with the protocol of IV Ach is a direct action on the M3 receptor--> dialation via NO release ----> reflex increase in HR.

With B the flow of reasoning is linear and forward (cause --> effect) and with D its the opposite (effect ---> cause).

How do you guys decide what the answer is between these 2?
M3 doesnt act on the arterioles(vasculature)... only---gland, gut, bladdder,bronchioles,miosis-pupilary sphicnter contraction, accomodation-ciliary contraction
M3 is Gq.

beta 2 would cause vasodialation
 

·
Registered
Joined
·
15 Posts
M3 receptors CAN cause vasodilation through Gq coupled stimulation of NO synthase in the endothelial cells. This activation produces NO in the endothelial cells which diffuse into the smooth muscle cells. In the smooth muscle cell they activate Guanylyl cyclase to produce cGMP from GTP. cGMP (like cAMP) increases levels of PKD. As it suggests, this is a protein kinase and therefore phosphorylates a phophotase to activate it. This phosphotase DE-phophorylates Myosin Light Chain. We all know that Myosin light chain requires phosphorylation for binding the ATP required for myosin/actin interaction. So basically the relaxation is achieved through NO production mediated by GTP/cGMP.

These SAME Gq coupled system is used also by Bradykinin and H1 receptors on vessels!

Gq can also cause vaconstriction but this is mediated through the classic Ca/calmodulin binding we all learned about. These Gq system is coupled to M3 receptors as well but these are in the LUNGS and therefore cause CONSTRICTION. Same Gq is also used by alpha-1 recetors to achieve their vasoconstrictive effects.

Now that the receptor coupling is explained, this vasodilation decreases TPR leading to increased sympathetic activation causing a subsequent increase in HR while having an overall lower TPR. I know there are also alpha 1 receptors in the vessels but i'm not sure why this wouldn't simply bring TPR back up to a normal level as opposed to an overall decrease. In either case, hope the post receptor mechanism cleared up some confusions. Please correct me if i'm wrong! :)
 

·
Registered
Joined
·
15 Posts
For the question regarding HOW Nitric Oxide synthase is activated by Gq, remember that this Gq receptor is on and endothelial cell unlike the Gq receptors on smooth muscle cells in the lung. Although the Gq receptor STILL raises Calcium in the cell through IP3/Dag system, the increased calcium is associated with completely different downstream effects. In this case, there are many ISOFORMS of nitric oxide synthase. The isoform in the endothelial cells is called eNOS and is activated by calcium.
 

·
Registered
Joined
·
116 Posts
M3 receptors CAN cause vasodilation through Gq coupled stimulation of NO synthase in the endothelial cells. This activation produces NO in the endothelial cells which diffuse into the smooth muscle cells. In the smooth muscle cell they activate Guanylyl cyclase to produce cGMP from GTP. cGMP (like cAMP) increases levels of PKD. As it suggests, this is a protein kinase and therefore phosphorylates a phophotase to activate it. This phosphotase DE-phophorylates Myosin Light Chain. We all know that Myosin light chain requires phosphorylation for binding the ATP required for myosin/actin interaction. So basically the relaxation is achieved through NO production mediated by GTP/cGMP.

These SAME Gq coupled system is used also by Bradykinin and H1 receptors on vessels!

Gq can also cause vasodilation but this is mediated through the classic Ca/calmodulin binding we all learned about. These Gq system is coupled to M3 receptors as well but these are in the LUNGS and therefore cause CONSTRICTION. Same Gq is also used by alpha-1 recetors to achieve their vasoconstrictive effects.

Now that the receptor coupling is explained, this vasodilation decreases TPR leading to increased sympathetic activation causing a subsequent increase in HR while having an overall lower TPR. I know there are also alpha 1 receptors in the vessels but i'm not sure why this wouldn't simply bring TPR back up to a normal level as opposed to an overall decrease. In either case, hope the post receptor mechanism cleared up some confusions. Please correct me if i'm wrong! :)
Yeap you are right. I had that memorized from FA, but I just checked Kaplan, it does include M3. effing FA! And your mechanism is right on. :)
 

·
Registered
Joined
·
27 Posts
Thats all fine and dandy, you guys are all right on the mechanism of action, but thats not really what I am trying to get at. If we assume that everything is correct with the mechanisms how do you decide the right answer. B and D are basically 2 halves of a complete answer.

So basically if you do what B says you will get D as a response. If you observe D then you can conclude B happened.
 

·
Registered
Joined
·
11 Posts
B is the right answer.
Ach is usually parasympathetic in action and we can see its constrictive effect in bronchospasm wherein it increases calcium in the smooth muscles through stimulation of M3, Gq alpha subunit, activation of phospholipase c and increase of inositol triphosphate and calcium, activation of phosphokinase c and its effects ( smooth muscles contraction)

However Ach is famous for having a paradoxical effect on vascular tone and bronchiolar tone. In vascular endothelium M3 activation stimulates NO formation,whiohc diffuses to adjacent smooth muscles and causes vasodilation.

This decreases MAP and reflexly increases heart rate. But the question is intended to test knowledge of paradoxical effect of ACh on Bronchiolar tone and vascular tone.
 

·
Registered
Joined
·
11 Posts
Interestingly if we apply this Ach to the sinoatrial node, it will prolong the phase 4 (slow depolarization) and slow down the heart rate!
MOA : it increases the efflux of K (conductance is increased)so that cell surface remains negative for more time. and it blocks calcium channels,so depolarization at SA node is further slowed down.
it also increases the AV node conduction delay.
What is AV nodal delay? Give its causes

Ans.
Definition: AV node is responsible for the delay in transmission of impulse generated in SA node. This delay in impulse transmission is called AV nodal delay. It is about 0.09 second.
Causes:
Junctional fibers of AV node are very small in size.
Resting membrane potentials of these fibers are much negative than the normal resting membrane potential of cardiac muscle.
Very few gap junctions connect the successive fibers in the pathway, so that there is great resistance to the conduction of excitatory ions from one fiber to the next.
Prolonged refractory period of AV node.
 
1 - 18 of 18 Posts
Top