Lessons from rat models of hypertension: from Goldblatt to genetic engineering

Area of Science:

• Cardiovascular Research
• Animal Models of Disease
• Pharmacology

Background:

• Hypertension research extensively utilizes rat models, with the spontaneously hypertensive rat (SHR) being the most common.
• The SHR model primarily represents a rare subtype of human hypertension (Mendelian-inherited primary hypertension).
• Other rat models capture diverse etiological aspects of hypertension but are less frequently employed.

Purpose of the Study:

• To review the utility of various rat models in hypertension research.
• To compare the natural history and drug responses across different hypertension models.
• To assess the impact of model selection on understanding hypertension's end-organ damage and treatment.

Main Methods:

• Comparative analysis of multiple rat models: SHR, Dahl, deoxycorticosterone acetate (DOCA)-salt, two-kidney one-clip, and transgenic TGR(mRen2)27.
• Evaluation of cardiac hypertrophy, endothelial function, and end-organ damage (heart failure, stroke, kidney failure) across models.
• Assessment of antihypertensive drug efficacy, including dose-dependency and class-specific effects.

Main Results:

• All models exhibit cardiac hypertrophy and impaired endothelium-dependent relaxations.
• Severe end-organ damage varies significantly among models and individuals.
• Antihypertensive efficacy depends on blood pressure reduction; some drugs are model-specific (e.g., endothelin-receptor antagonists in DOCA-salt vs. SHR).

Conclusions:

• End-organ damage is influenced by blood pressure stress, biochemical factors, and the organism's 'coping' mechanisms.
• Failure to recruit adequate coping mechanisms may signify increased risk.
• Transgenic techniques offer future potential for developing models that better balance stress and coping in hypertension research.