sympathetic effect on PVR help!!!

[RossDocGunnab]

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hey folks,

2nd yr med student at Ross University.....

we're doin autonomic drugs and i am kinda confused about determinants of PVR. figured i'd try u guys b4 approaching faculty on monday.

so here goes:
skeletal muscle arteriolar smooth muscle has more b2 than a1 receptors. therefore, an IV bolus of epinephrine causes dilation of these arterioles. in fact, goodman and gillman says that sympathetic stimulation in skeletal muscle causes overall dilation.

because skeletal muscle accounts for about 45% of body weight in the average person, the vascular resistance within skeletal muscle would make up the major determinant of resistance in the total vasculature.

this is evident by:
IV bolus of epinephrine causes a decrease in PVR.
during exercise, PVR is also decreased.
in the above two conditions, the PVR is decreased in spite of the fact that skin and splanchnic arterioles are constricted. this is because the PVR is mainly determined by skeletal vascular resistance.

so here is my confusion:
according to goodman and gillman and other resources, sympathetic stimulation in the resting subject and nicotine poisoning both cause an increase in PVR!!!😱
how is that the case? the body is flooded with epi and norepi in these cases, causing dilation in skeletal muscle, no?
can anyone elaborate.

thanx

 

[The right Path]

Short and sweet answer- your arteries/arterioles have smooth, not skeletal muscle.

 

[RossDocGunnab]

Short and sweet answer- your arteries/arterioles have smooth, not skeletal muscle.

thanx for the input but i dont think u read or understood the question. as a 2nd yr, i am perfectly aware that vessels have smooth muscle, not skeletal. i actually directed the question to other med students, not premeds.

 

[tmac11]

Norepinephrine does not act on B2 receptors (as those are not innervated and NE is a neurotransmitter) so it acts to increase PVR due to its action on A1 receptors (among other actions at B1). Epinephrine's actions slightly differ based on its dose. With a low dose, epinephrine acts similar to a non-selective beta agonist (B1 and B2), such as isoproterenol. With a high dose, epinephrine acts on A1, B1, and B2. The A1 action of epinephrine (in a high dose) will mask the B2 action, making it act similar to norepinephrine. So with sympathetic stimulation, the actions of NE and a high dose of epinephrine (acting like NE) will lead to a predominant A1 stimulation that will mask the effects of B2 stimulation --> overall increased PVR. Hope this helps.

 

[The right Path]

thanx for the input but i dont think u read or understood the question. as a 2nd yr, i am perfectly aware that vessels have smooth muscle, not skeletal. i actually directed the question to other med students, not premeds.

You're right, I just skimmed the question and jumped to conclusions, my bad.

 

[turkeyjerky]

Norepinephrine does not act on B2 receptors (as those are not innervated and NE is a neurotransmitter) so it acts to increase PVR due to its action on A1 receptors (among other actions at B1). Epinephrine's actions slightly differ based on its dose. With a low dose, epinephrine acts similar to a non-selective beta agonist (B1 and B2), such as isoproterenol. With a high dose, epinephrine acts on A1, B1, and B2. The A1 action of epinephrine (in a high dose) will mask the B2 action, making it act similar to norepinephrine. So with sympathetic stimulation, the actions of NE and a high dose of epinephrine (acting like NE) will lead to a predominant A1 stimulation that will mask the effects of B2 stimulation --> overall increased PVR. Hope this helps.

This is right. Also wanted to add that the decreased resistance of PVR during exercise is primarily due to local vasodilatory agents produced by the exercising muscles (adenosine, etc), not sympathetic drive.

 

[RossDocGunnab]

This is right. Also wanted to add that the decreased resistance of PVR during exercise is primarily due to local vasodilatory agents produced by the exercising muscles (adenosine, etc), not sympathetic drive.

i understand that. i made the exercise point to empasize the role of skeletal muscle resistance as a determinant of overall PVR.

 

[RossDocGunnab]

Norepinephrine does not act on B2 receptors (as those are not innervated and NE is a neurotransmitter) so it acts to increase PVR due to its action on A1 receptors (among other actions at B1). Epinephrine's actions slightly differ based on its dose. With a low dose, epinephrine acts similar to a non-selective beta agonist (B1 and B2), such as isoproterenol. With a high dose, epinephrine acts on A1, B1, and B2. The A1 action of epinephrine (in a high dose) will mask the B2 action, making it act similar to norepinephrine. So with sympathetic stimulation, the actions of NE and a high dose of epinephrine (acting like NE) will lead to a predominant A1 stimulation that will mask the effects of B2 stimulation --> overall increased PVR. Hope this helps.

hey thanx for the input. B2 receptors however ARE in the same location as a1 on the smooth myocyte, they dont get activated by NE because NE does not bind them. also the actions of low dose epi are not like those of isoprotenerol. epi regardless of dose will increase both mean BP and HR. while isoproterenol decreases BP and increases HR.

also, low dose epi (causing a mild reduction in PVR) does not seem to act like a non-select B agonist (causing a moderate reduction in PVR) because low dose epi is still binding a1 receptors. moreover, first aid mentions that selectivity of epi at low dose would be b1, not b2.

now let us assume that first aid is wrong and that indeed, during sympathetic upshoot (high doses epi), epi would result in a1 masking b2 and an overall constriction or no change in skeletal muscle arterioles; in this scenario, according to your reasoning, sympathetic upshoot would cause skeletal muscle arteriolo-constriction. but according to goodman and gillman, sympathetic stimulation causes DILATION of skeletal muscle arterioles, due to the presence of more b2 receptors than a1 in skeletal muscle...table 8-1 (http://accessmedicine.com/content.aspx?aID=16661345).

again, i'd like to thank those who attempted to clarify the issue....if i come up with an answer i will post it here