Table 1.

Common animal models for hypertension with different etiology.

Experimental model	Description
Genetic hypertension    (i) SHR    (ii) Dahl salt-sensitive    (iii) Transgenic	(i) SHR is developed by inbreeding Wistar rats (brother-to-sister) with the highest BP [28]. The BP increases at week 4 to week 6 and reach systolic BP of 180–200 mmHg [28]. SHR may develop cardiac hypertrophy, cardiac failure, renal dysfunction, and impaired endothelium-dependent relaxations [60–62]. (ii) Dahl salt-sensitive rats derived from Sprague-Dawley rats on the basis of administering high NaCl diet. Salt-sensitive rats become hypertensive when given normal salt diets; however these rats develop severe and fatal hypertension with high salt diet (8% NaCl) [32]. These rats may develop cardiac hypertrophy, severe cardiac failure, hypertensive nephropathy, impaired endothelium-dependent relaxations [63–65]. (iii) Transgenic model can be generated by overexpression of a specific gene, for example, the mouse Ren-2 gene, and TGR(mREN2)27 [66]. Manifestations include marked cardiac hypertrophy, moderate proteinuria, and impaired endothelium-dependent relaxations [67, 68].
Endocrine hypertension	(i) Administration of DOCA in a combination with high salt diet and unilateral nephrectomy [69]. (ii) DOCA-induced hypertension induces a low renin model of hypertension [70]. (iii) Increased cardiac weight, proteinuria, glomerulosclerosis, and impaired endothelium-dependent relaxations [71, 72].
Environmental hypertension	(i) Stress-induced hypertension using flashing lights, loud noise, restraint cage, and cold or hot stimuli [73, 74]. (ii) Activation of sympathetic nervous system and RAAS may contribute to the initiation of stress-induced hypertension [75, 76].
Pharmacological hypertension	(i) Nitric oxide-deficient model by administering NOS inhibitors such as L-NAME [77]. (ii) Increase in BP was reported during long-term oral treatment with NOS inhibitors [78, 79]. (iii) Development of endothelial dysfunction is gradually with increased of BP [80].
Renal hypertension	(i) This includes two-kidney one-clip hypertension (2K1C; constriction of one renal artery while the contralateral kidney is left intact), one-kidney one-clip hypertension (1K1C; one renal artery is constricted and the contralateral kidney is removed), and two-kidney two-clip hypertension (2K2C; constriction of aorta or both renal arteries) [81, 82]. (ii) In the two-kidney model, circulating renin and aldosterone levels are increased [83], which are most notably in the early phase of hypertension [84].

SHR: spontaneously hypertensive rat; BP: blood pressure; NaCl: sodium chloride; TGR: transgenic rat; RAAS: renin-angiotensin-aldosterone system; DOCA: deoxycorticosterone acetate; NOS: nitric oxide synthase; L-NAME: N^ω-nitro-L-arginine methyl ester.