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U22203 (Respiratory, Renal & Cardiovascular Pharmacology): general guide to coursework marking criteria Q1. Answer should include e.g. pharmacological natures of the reagents, sites of action, relevant receptors occupied and the involvement of any relevant endothelium derived mediators and any relevant major second messengers in dilator mechanisms Q2 Answer should include e.g. pharmacological natures of the reagents, sites of action, relevant receptors occupied and the involvement of any relevant major second messengers in dilator mechanisms Q3. Answer should include e.g. consideration of relevant phase(s) of relevant cardiac action potential/sites of action, relevant receptors occupied and signalling events including the involvement of any relevant second messengers Q4. Answer should include e.g. consideration of chemical as well as pharmacological natures of these reagents Q5. Answer should include e.g. consideration of relevant phases of relevant cardiac action potentials/sites/types of action, relevant receptors occupied and signalling events including the involvement of any relevant second messengers as well as overall rank potency order for these reagents re raising heart rate and force Q6. Answer should include e.g. consideration of relevant phases of relevant cardiac action potentials/sites/types of action, relevant ion channels and relevant mechanisms of excitation-contraction coupling re effects on cardiac force Q7. Answer should include e.g. consideration of pharmacological nature of ouabain, major site and mechanism of action in vitro and relevant related cellular chain of events with significance for cardiac force Q8. Answer should include e.g. consideration of pharmacological nature of verapamil, consideration of relevant phase(s) of relevant cardiac action potential/site(s) of action and mechanism of action, including effects on relevant ion movement(s) Q9. Answer should include e.g. consideration of electrical nature of stimulus and relevant mechanisms of action/outcomes for relevant cardiac ion channels and ion movements and excitability Q10. Answer should include e.g. consideration of pharmacological nature of propranolol and expected interaction with autonomic nervous regulation of cardiac function, as e.g. in a whole organism Q11. Answer should include e.g. consideration of other relevant biological/functional attributes of a whole organism (in vivo) which could affect pharmacological responses, the influence of which would be avoided by using an in vitro preparation Q12. The numerical estimate supplied should represent EC50 in µM NB: references are optional, but not required Microsoft Word - U22203 coursework 2019-2020 re first attempt U22203 (Respiratory, Renal & Cardiovascular Pharmacology): coursework Please submit completed coursework as word document (≤ 1000 words) online by end of Friday, January 10, 2020. NB: Ensure to enter your student number in both filename of submitted document and in document itself. Q1. Briefly describe the mechanism of vasodilation to carbachol and phentolamine in the endothelium-intact, phenylephrine- preconstricted isolated aorta. (10%) Q2. Briefly describe the mechanism of relaxation to salbutamol and atropine in the carbachol-precontracted isolated trachea. (10%) Q3. Briefly explain the effects of acetylcholine on heart rate, at a cellular signalling level, in the isolated perfused heart. (15%) Q4. Comment on why the use of carbachol in place of acetylcholine is sometimes preferred experimentally. (5%) Q5. At a cellular signalling level, how do ß-adrenoceptor agonists raise heart rate and force of contraction in the isolated perfused heart and what is the expected relative order of potency of noradrenaline, adrenaline and isoprenaline with respect to cardiac effects? (20%) Q6. Briefly explain the importance of calcium to both heart rate and force of contraction in the isolated perfused heart. (10%) Q7. Briefly explain the effects of ouabain to raise the force of contraction in the isolated perfused heart. (5%) Q8. Briefly explain how verapamil is able to reduce the force of contraction in the isolated perfused heart. (5%) Q9. Briefly explain how high potassium can arrest the heart in diastole in the isolated perfused heart. (5%) Q10. Describe how the presence of an intact autonomic nervous system might have altered the response to propranolol per se in the isolated perfused heart. (5%) Q11. Apart from an intact nervous system, name two more key, physiologically relevant in vivo features that are typically absent from in vitro preparations. (5%) Q12. Using data in table 1, estimate the EC50 value for carbachol in µM, from a plot of the sigmoidal concentration-response curve. (5%) Table 1. Contraction in the isolated trachea in response to carbachol (CCh) (n=1) Log10 [CCh] (M) in organ bath contraction (g) -8 0 -7.52 0.05 -7 0.3 -6.52 0.5 -6 1.2 -5.52 2.3 -5 3.25 -4.52 3.5 -4 3.5