Screening models for cardiovascular drugs—antihypertensives are vital for B.Pharm students to evaluate drug efficacy, safety, and mechanisms affecting blood pressure. This overview highlights in vitro and in vivo models: isolated tissue preparations (aortic rings, wire myograph, Langendorff heart), cell-based assays (HUVEC, vascular smooth muscle cells), and animal models (SHR, DOCA-salt, two-kidney one-clip). Key terms include pharmacodynamics, pharmacokinetics, dose–response, EC50/IC50, receptor binding, telemetry, and high-throughput screening. Students should grasp assay selection, interpretation of vasorelaxation/constriction data, target engagement (ACE, AT1, β-adrenergic, Ca2+ channels), and translational limitations. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which preparation is most commonly used to study endothelium-dependent vasorelaxation in antihypertensive screening?
- Isolated rat aortic ring (organ bath preparation)
- Langendorff perfused heart
- Tail-cuff blood pressure in conscious rat
- hERG channel assay
Correct Answer: Isolated rat aortic ring (organ bath preparation)
Q2. Which animal model is a genetic model of hypertension frequently used for long-term antihypertensive studies?
- Spontaneously hypertensive rat (SHR)
- DOCA-salt rat
- Two-kidney one-clip (2K1C) rat
- Normal Wistar rat
Correct Answer: Spontaneously hypertensive rat (SHR)
Q3. Which assay directly measures myocardial contractile function ex vivo for screening cardioactive antihypertensive effects?
- Langendorff isolated perfused heart
- Wire myograph for small arteries
- HUVEC NO production assay
- Tail-cuff plethysmography
Correct Answer: Langendorff isolated perfused heart
Q4. In organ bath studies, which agent is commonly used to precontract vascular tissue before testing vasorelaxants?
- Phenylephrine (α1-agonist)
- Amlodipine (calcium channel blocker)
- Angiotensin II receptor blocker
- Acetylcholine (endothelium-dependent vasodilator)
Correct Answer: Phenylephrine (α1-agonist)
Q5. Which cell type is most appropriate to study endothelial function and nitric oxide–mediated vasodilation in vitro?
- Human umbilical vein endothelial cells (HUVECs)
- Cardiomyocytes
- Hepatocytes
- Renal proximal tubular cells
Correct Answer: Human umbilical vein endothelial cells (HUVECs)
Q6. What parameter derived from a dose–response curve indicates drug potency in vasorelaxation studies?
- EC50 (effective concentration for 50% response)
- Maximal response (Emax)
- Therapeutic index
- Half-life (t1/2)
Correct Answer: EC50 (effective concentration for 50% response)
Q7. Which in vivo technique provides continuous, high-fidelity arterial blood pressure measurement in conscious rodents for antihypertensive evaluation?
- Telemetry implant
- Tail-cuff method
- Non-invasive oscillometry
- Single-point catheterization under anesthesia
Correct Answer: Telemetry implant
Q8. Which model is induced by mineralocorticoid excess plus salt and is used to study salt-sensitive hypertension?
- DOCA-salt model
- SHR model
- Two-kidney one-clip (2K1C)
- β-adrenergic overstimulation model
Correct Answer: DOCA-salt model
Q9. For assessing blockade of L-type calcium channels in vascular smooth muscle, which in vitro approach is most appropriate?
- Patch-clamp recording on VSMCs
- HUVEC proliferation assay
- Renin activity assay
- hERG potassium current assay
Correct Answer: Patch-clamp recording on VSMCs
Q10. In a Schild analysis, a parallel rightward shift of the agonist dose–response curve without change in Emax indicates what type of antagonism?
- Competitive (surmountable) antagonism
- Non-competitive antagonism
- Irreversible antagonism
- Partial agonism
Correct Answer: Competitive (surmountable) antagonism
Q11. Which biochemical assay would you use to quantify ACE inhibition in vitro during antihypertensive screening?
- Hippuryl–histidyl–leucine hydrolysis assay (ACE activity assay)
- cAMP ELISA
- Western blot for β1-receptor
- Renal clearance measurement
Correct Answer: Hippuryl–histidyl–leucine hydrolysis assay (ACE activity assay)
Q12. Which preclinical screening is essential to detect potential QT prolongation liability of a new antihypertensive?
- hERG channel inhibition assay
- P450 induction screen
- Renin activity assay
- Organ bath aortic relaxation
Correct Answer: hERG channel inhibition assay
Q13. In radioligand binding assays for angiotensin II receptors, what does a decrease in radioligand binding indicate when testing a candidate drug?
- Competitive displacement indicating receptor affinity of the drug
- Increased receptor expression
- Enzymatic degradation of ligand
- Non-specific binding artifact
Correct Answer: Competitive displacement indicating receptor affinity of the drug
Q14. Which in vivo model best mimics renovascular hypertension for testing renin–angiotensin system inhibitors?
- Two-kidney one-clip (2K1C) model
- DOCA-salt model
- SHR model
- Dahl salt-sensitive rat
Correct Answer: Two-kidney one-clip (2K1C) model
Q15. Which experimental stimulus is often used to test endothelium-independent vasodilation mediated by smooth muscle relaxation?
- Sodium nitroprusside (NO donor)
- Acetylcholine (endothelium-dependent)
- Phenylephrine (vasoconstrictor)
- Bradykinin (endothelium-dependent)
Correct Answer: Sodium nitroprusside (NO donor)
Q16. For high-throughput screening of antihypertensive leads targeting ACE, which platform is most suitable?
- Fluorescence-based enzymatic ACE inhibition assay
- Langendorff heart preparation
- Telemetry blood pressure recording
- Wire myograph organ bath
Correct Answer: Fluorescence-based enzymatic ACE inhibition assay
Q17. Which parameter indicates the safety margin between effective and toxic doses in preclinical pharmacology?
- Therapeutic index (TI)
- IC50 for target binding
- EC50 for vasorelaxation
- Pearson correlation coefficient
Correct Answer: Therapeutic index (TI)
Q18. Which in vitro model allows measurement of vascular reactivity in small resistance arteries relevant to peripheral resistance regulation?
- Wire myograph
- Langendorff heart
- HUVEC tube formation
- HEK293 cell transfection
Correct Answer: Wire myograph
Q19. Which pharmacokinetic parameter is most important to ensure adequate exposure of an antihypertensive drug in chronic studies?
- Area under the plasma concentration–time curve (AUC)
- Maximum binding affinity (Kd)
- Number of hydrogen bond donors
- In vitro IC50
Correct Answer: Area under the plasma concentration–time curve (AUC)
Q20. Which off-target screen is critical to minimize adverse metabolic–drug interaction risks for new antihypertensives?
- CYP450 enzyme inhibition/induction panel
- Langendorff heart assay
- Wire myograph constriction assay
- Endothelial NO synthesis assay
Correct Answer: CYP450 enzyme inhibition/induction panel
Q21. During organ bath studies, removal of the endothelium abolishes which response to acetylcholine?
- Endothelium-dependent vasodilation
- Sodium nitroprusside–induced relaxation
- Phenylephrine-induced contraction
- Baseline passive tension
Correct Answer: Endothelium-dependent vasodilation
Q22. Which in vivo measurement is commonly used to estimate plasma renin activity in antihypertensive research?
- Radioimmunoassay or ELISA for angiotensin I generation
- ECG recording
- Urine sodium concentration only
- hERG channel current measurement
Correct Answer: Radioimmunoassay or ELISA for angiotensin I generation
Q23. In vascular smooth muscle, blocking which target produces rapid vasodilation by preventing Ca2+ influx?
- L-type calcium channels
- ACE enzyme
- AT1 receptor
- eNOS enzyme
Correct Answer: L-type calcium channels
Q24. Which screening approach helps predict human relevance early by assessing target binding and potential off-target interactions computationally?
- In silico molecular docking and ADMET prediction
- Langendorff perfusion
- Wire myograph of rat mesenteric arteries
- HUVEC proliferation assay
Correct Answer: In silico molecular docking and ADMET prediction
Q25. Which method is best for measuring acute baroreflex-mediated changes in heart rate during antihypertensive testing?
- Telemetry with synchronized blood pressure and ECG
- Tail-cuff plethysmography
- Organ bath aortic relaxation
- Western blot for β1 receptor protein
Correct Answer: Telemetry with synchronized blood pressure and ECG
Q26. Which model is most appropriate to evaluate endothelial dysfunction induced by chronic high salt intake?
- Dahl salt-sensitive rat
- SHR rat
- 2K1C rat
- Normal Sprague–Dawley rat on standard diet
Correct Answer: Dahl salt-sensitive rat
Q27. For assessing direct renin inhibitors, which assay provides direct measurement of renin catalytic function?
- Renin activity assay measuring angiotensin I production
- NO production assay in endothelial cells
- hERG inhibition assay
- Wire myograph constriction test
Correct Answer: Renin activity assay measuring angiotensin I production
Q28. Which experimental readout indicates a drug is an ARB (angiotensin II type 1 receptor blocker) in receptor pharmacology studies?
- Competitive displacement of angiotensin II radioligand at AT1 receptor
- Inhibition of L-type Ca2+ current in cardiomyocytes
- Direct stimulation of NO release from endothelium
- Activation of β-adrenergic receptor signaling
Correct Answer: Competitive displacement of angiotensin II radioligand at AT1 receptor
Q29. When comparing two antihypertensive compounds, which metric helps compare intrinsic efficacy at producing maximal vasodilation?
- Maximal response (Emax)
- EC50 alone
- Clearance (CL)
- LogP value
Correct Answer: Maximal response (Emax)
Q30. Which ethical consideration is most relevant when selecting animal models for chronic antihypertensive efficacy studies?
- Refinement, reduction, and replacement (3Rs) and minimizing animal suffering
- Only cost of animals
- Publishing in high-impact journals
- Maximizing number of interventions per animal regardless of welfare
Correct Answer: Refinement, reduction, and replacement (3Rs) and minimizing animal suffering
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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