Endothelium in Health and Disease

Topics: Endothelium, Blood vessel, Muscarinic acetylcholine receptor Pages: 4 (893 words) Published: December 13, 2012
Investigation of the influence of the endothelium on the actions of acetylcholine and nitroprusside.

(a) Estimate the maximum responses (Emax) and EC50 values for phenylephrine with the two types of arterial ring. Put this data in a single, self-explanatory table.

Table1. Emax and EC50 values for phenylephrine.
Phenylephrine| Emax in grams tension| EC50 in nM|
Endothelium intact| 2.2| 40|
Endothelium denuded| 2.9| 10|

(c) Estimate the EC50 values for the effects of acetylcholine and nitroprusside in both types of arterial ring, and present these in a table.

Table 2. EC50 values for the effect of acetylcholine and nitroprusside. EC50 in nM| Endothelium intact| Endothelium denuded| Acetylcholine | 40| 00|
Nitroprusside | 5| 0.6|

d) Why was the standard concentration of phenylephrine taken at 90% of the maximum response, rather than 100%?

Increasing concentrations enhances the fractional occupancy of the drug. The dose concentration curve gets closer to the top plateau but never reaches it. As a result there can be no EC100. (GraphPad Software, 2012). It was relevant to determine 90% concentration, which is a submaximal value, of phenylephrine from the individual dose-response curve and use it as a standard concentration.

e) Give one possible explanation as to why the Emax and EC50 values for phenylephrine are different in rings with and without endothelium.

The concentration of phenylephrine required to reach Emax and EC50 values in cells with intact endothelium was almost four times higher than in endothelium denuded preparations. As a response to a variety of chemical and physical stimuli an endothelium spontaneously releases numerous dilator factors called EDRF-endothelium derived relaxing factor (Furchgott and Zawadzki in 1980.)

An exposure of endothelium intact preparation to a various...
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