[dun13203171]

Hi guys.
            So we obtained results from a previously done experiment and they are not what I expected.

response was measured at varying concentrations of norepinephrine in tissue with endothelium present and one without endothelium.

Without endothelium a higher tissue  response was observed, I am not sure why apart from possible greater expression of b1 receptors?

ACh was then added to a bath containing the conc of norepinephrine that produced maximal response. This was done with endothelium and without.

I observed 0 response for the tissue with endothelium, I understand that Ach bind muscarinic 3 receptors and stimulate Nitric oxide release and thus vasodilation. What I don't understand is how this completely inhibits norepinephrine from illicit even just a small effect??

Contrastingly, in the tissue without endothelium , ACh produced an increase in response to that of norepinephrine on its own. This I am struggling to explain, what receptor did ACh target in this case and how did it enhance sympathetic activity of norepinephrine??


Thanks in advance

[pgk]

Obviously, blocking β1 and β2 receptors of endothelian cells inhibits any further adrenergic tissue response. If this is the case, higher norepinephrine concentration does not help because this simply leads to saturation of endothelian β1 and β2 receptors. Besides, both norepinephrine (logP = -0.88, logD= -2.65_pH = 7.5) and acetylcholine (logP = -0.39, logD= -3.5_pH = 7.5) are hydrophilic molecules and cannot passively cross endothelium (by the exception of sinusoid endothelium) that is a lipophilic barrier.