Some Exercises for the Computer Program "CARDIOLAB"
Contact: Sven Tågerud, Department of Natural Sciences, University of Kalmar, SE-391 82 Kalmar, Sweden. HYPERLINK mailto: , tel +46-480-446256; fax +46-480-446262.
1. Use a normal rat. Study the effects of adrenaline using doses of 0.5, 1, 5, 10 and 100 nmole/kg.
Question: Why does the blood pressure change in different directions after different doses of adrenaline?
Comments: This experiment demonstrates that low doses of adrenaline mainly affect beta receptors giving a decrease in blood pressure and increased heart rate. At higher doses an increase in blood pressure is seen due to activation of alpha receptors. Also note the time course after larger doses. As adrenaline is eliminated from the circulation the concentration decreases and the increase in blood pressure is followed by a decrease since the beta2 receptors have higher affinity for adrenaline than the alpha receptors.
2. Treat the rat with prpopranolol 5000 nmole/kg and repeat the different adrenaline doses. Question: Do the results agree with your explanation above?
Comments: At doses up to 10 nmole/kg adrenaline will only cause an increase in blood pressure as expected. At the highest dose beta receptor effects of adrenaline (increased heart rate and decreased blood pressure at the end of the adrenaline effect) are also seen due to the competitive nature of the beta blockade obtained with propranolol.
3. Choose a new normal rat. Repeat the different adrenaline doses to make sure this rat responds like the previous one. Next treat the rat with prazosin 2000 nmole/kg and repeat the different adrenaline doses. Explain the results.
Comments: This demonstrates adrenaline reversal. All adrenaline doses (except the highest) only give decreases in blood pressure due to activation of beta2 receptors. The highest dose gives a small increase in blood pressure due to competition with the alpha blocker.
4. Repeat all the above (1-3) using noradrenaline instead of adrenaline.
Question: Why do you see a decrease in heart rate when you give a high noradrenaline dose (100 nmole/kg) to a rat pretreated with propranolol 5000 nmole/kg)? (Hint: try the same in a pithed rat).
Comments: The experiments demonstrate that noradrenaline has no effect on beta2 receptors and thus never causes a decrease in blood pressure. The baroreceptor reflex (increased parasympathetic activity) causes the decreased heart rate after a high noradrenaline dose to a propranolol treated rat. This will not be observed in a pithed rat.
5. Try vasopressin at 2, 5, 10, 20 ,50 and 100 mIU/kg in a normal rat and in a pithed rat. Explain the difference in effects on heart rate.
Comments: Again high doses cause a decreased heart rate due to the baroreceptor reflex.
6. Try angiotensin at 0.2, 0.5, 1, 2, 5 and 10 nmole/kg.
Question: Does pretreatment with propranolol (5000 nmole/kg) or prazosin (2000 nmole/kg) affect the response to angiotensin and if so why?
Comments: It is usually informative to compare the angiotensin responses to the vasopressin responses and to try to figure out why the heart rate response is different for the two compounds. By pretreating with propranolol the angiotensin response becomes similar to the vasopressin response. The same can be seen by giving angiotensin to a reserpin treated rat. The effect of angiotensin on heart rate is thus dependent on the release of noradrenaline acting on beta receptors in the heart.
7. Repeat the angiotensin doses in a reserpine treated rat.
Question: How does this affect the heart rate response to angiotensin and why?
Comments: See above (6).
8. Choose a new normal rat. Test its response to relatively low doses of adrenaline (2 nmole/kg) and noradrenaline (2 nmole/kg). Give cocaine (10000 nmole/kg) to the rat and repeat the adrenaline and noradrenaline doses. Explain the results.
Comments: Demonstrates that the effects of systemic noradrenaline or adrenaline are potentiated after cocaine.
9. Examine whether or not cocaine affects the response to angiotensin or vasopressin.
Comments: Demonstrates that the effect of angiotensin on heart rate is potentiated by cocaine. There is no effect on the vasopressin response.