ggupta@technomedjournals.com
+91 70877 11159
logo

Journal of Development in Bioengineering and Biosciences

LoginTrack
Published

Evaluating the Limitations of Animal Models in Antihypertensive Drug

Disha Kalpesh Jain
ORCID

Published in ( April-June 2026) (Vol. 1, Issue 1, 2026)

Evaluating the Limitations of Animal Models in Antihypertensive Drug - Issue cover

Keywords

HypertensionAnimal modelsSpontaneously hypertensive ratThree RsTranslational researchiPSC-derived vascular modelsAntihypertensive drug developmentSex differences

Abstract

This report critically evaluates the principal animal models used in antihypertensive drug development and the systematic factors underlying the persistent gap between preclinical efficacy and clinical outcomes. Three model systems are examined, the spontaneously hypertensive rat (SHR), the Dahl salt-sensitive rat, and renovascular (two-kidney and one-kidney one-clip) models, assessing their experimental utility, translational limitations, and ethical implications against human essential hypertension. Although each has yielded foundational mechanistic insight and supported major drug classes, their collective predictive validity is constrained by genetic homogeneity, the absence of common comorbidities (obesity, type 2 diabetes, chronic kidney disease), a pronounced bias toward male-only cohorts, short experimental timeframes, and interspecies divergence in key signalling pathways. Inconsistent experimental design, particularly blood-pressure measurement method and under-reporting of animal sex, further erodes reproducibility and cross-study synthesis. The report situates these issues within the global research landscape, highlighting geographic and ancestry-related blind spots that limit relevance to under-represented populations, and within the Three Rs and current UK/EU regulatory and data-protection frameworks. Emerging bridging strategies, CRISPR-Cas9 models incorporating human-relevant blood-pressure QTLs, iPSC-derived vascular constructs and vessel-on-chip systems, and multi-omics integration with human cohort data are evaluated as routes to reducing translational attrition. It concludes that closing the translational gap requires not only better models but mandatory sex-disaggregated design, rigorous transparent reporting, validated comorbid models, and reform of regulatory and ethical review, an institutional challenge as much as a scientific one.

References

  1. [1]Lerman LO, Kurtz TW, Touyz RM, Ellison DH, Chade AR, Crowley SD, et al. Animal models of hypertension: a scientific statement from the American Heart Association. Hypertension. 2019;73(6):e87- e120. doi:10.1161/HYP.0000000000000090.
  2. [2]Afzal S, Attiq A, Wu YS, Alameen AO, Albokhadaim I, Kandeel M, et al. Evaluation of various experimental models in antihypertensive drug development: recent update. Int J Pharmacol. 2024;20(8):1350-64. doi:10.3923/ijp.2024.1350.1364.
  3. [3]Okamoto K and Aoki K. Development of a strain of spontaneously hypertensive rats. Jpn Circ J. 1963;27:282-293.
  4. [4]Jama HA, Muralitharan RR, Xu C, O'Donnell JA, Bertagnolli M, Broughton BRS, et al. Rodent models of hypertension. Br J Pharmacol. 2022;179(5):918-37. doi:10.1111/bph.15650.
  5. [5]McLoone VI, Ringwood JV and Van Vliet BN. A multi-component model of the dynamics of salt-induced hypertension in Dahl-S rats. BMC Physiol. 2009;9:20.
  6. [6]Martinez-Maldonado M. Pathophysiology of renovascular hypertension. Hypertension. 1991;17(5):707-19.
  7. [7]Pickering TG. Renovascular hypertension: etiology and pathophysiology. Semin Nucl Med. 1989;19(2):79-88.
  8. [8]Herrmann SM and Textor SC. Renovascular hypertension. Endocrinol Metab Clin North Am. 2019;48(4):765-78.
  9. [9]Drüeke TB and Devuyst O. Blood pressure measurement in mice: tail-cuff or telemetry? Kidney Int. 2019;95(5):1012-4. doi:10.1016/j.kint.2019.01.018.
  10. [10]Elmarakby AA and Sullivan JC. Sex differences in hypertension: lessons from the spontaneously hypertensive rat. Hypertension. 2021;78(4):1035-45.
  11. [11]Olivera S and Graham D. Sex differences in preclinical models of hypertension. J Hum Hypertens. 2023;37(8):619-25. doi:10.1038/s41371-022-00770-1.
  12. [12]Ferreira GS, Veening-Griffioen DH, Boon WPC, Moors EHM, van Meer PJK and Levitsky DO. Levelling the translational gap for animal to human efficacy data. Animals (Basel). 2020;10(7):1199.
  13. [13]Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-104. doi:10.1093/eurheartj/ehy339.

Authors (1)

Disha Kalpesh Jain
ORCID

University of Liverpool

View all publications →

Download Article

PDF

Best for printing and citation

File size: 0.4 MB
Format: PDF

Summarise this paper with AI:

GoogleGooglePerplexityPerplexityGrokGrokChatGPTChatGPTClaudeClaude

Article Information

Published in:

( April-June 2026) (Vol. 1, Issue 1, 2026)

JDBB110003

JDBB-01-000006

1-9

2026-06-27

JATS XML

Article Impact

Views:71
Downloads:10

How to Cite

Kalpesh D. Evaluating the Limitations of Animal Models in Antihypertensive Drug. Journal of Development in Bioengineering and Biosciences. 2026;1(1):1-9. Available from: https://jdbb.technomedjournals.com/articles/JDBB110003

Article Actions

Whatsapp