3.1. Spontaneous Hypertension Model

Spontaneously hypertensive rat (SHR) is a well model of hereditary hypertension and hypertensive cardiomyopathy [5]. The most commonly used experimental animal is a Wistar inbred rat cultivated by Okamoto in 1963. The spontaneous hypertension in this model is high, which is closely related to the activation of renin-angiotensin-aldosterone system (RASS) [6].

Generally 4 weeks after birth in rats, blood pressure will be significantly increased and left ventricular hypertrophy will occur, which was characterized by an increased left ventricular mass/weight body [7]. At 10 weeks, myocardial collagen content increased significantly [8]. Over time, the rat's heart contraction function gradually decreased, and diastolic dysfunction occurred 3 months later [7]. With the increase of cardiomyocyte hypertrophy and myocardial fibrosis, cardiomyocyte changes from stable hypertrophy to decompensation [5, 9, 10]. At about 18 months of age, SHR begin to show signs of heart failure, and by 24 months of age, more than 50% of rats have developed heart failure [9].

SHR model develops into hypertension and myocardial fibrosis under natural conditions without any artificial intervention and its progression of cardiac remodeling to heart failure is similar to that of humans [11]. Thus, they are more inclined to study genetic determinants and pathophysiological changes in disease progression [12]. However, the utility of the SHR in studying human hypertensive heart disease has been questioned because a genetic locus in SHR affects LV mass independent of blood pressure [13].