Imatinib Mesylate Attenuates Cardiac Fibrosis in Spontaneously Hypertensive Rats

Tianma Gouteng Decoction (TGD) is widely used in traditional Chinese medicine for the treatment of hypertension and its related complications, but its mechanisms remain incompletely defined. We now aim to assess the protective effect of TGD against cardiovascular damage and to investigate its characteristics and underlying mechanisms. Blood pressure was determined in TGD-treated spontaneously hypertensive rats (SHR) by noninvasive measurements. Echocardiography was performed to assess cardiac function and structure and sirius red staining to evaluate cardiac fibrosis, and the degree of vascular remodeling was evaluated. Additionally, vasoconstriction and relaxation factor expression changes were examined by means of ELISA. Protein expression changes were verified by western blot. Compared with untreated SHR, TGD-treated SHR exhibited cardiovascular traits more akin to those of the normotensive Wistar Kyoto (WKY) rats. That is, they had lower diastolic blood pressure, systolic blood pressure and mean BP, and increased expression of vasodilation factor. We also found that TGD reduces ventricular and vascular remodeling and improves cardiac function in SHR. Finally, we tested the antiapoptosis effect TGD exerts in SHR, ostensibly by upregulating the expression of OPG, TRAIL, and death receptor 5 (DR5) and downregulating caspases 8, 7, and 3. TRAIL may also exert antiapoptotic and prosurvival effects by upregulating AKT expression. Therefore, TGD may reverse cardiovascular remodeling in SHR by upregulating the expression of OPG and TRAIL, upregulating AKT, and inhibiting apoptosis, at least in part. For the first time, we have shown that OPG and TRAIL play complimentary cardioprotective roles in SHR.

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Effect of ramipril on the cardiac fibrosis in the left ventricle of spontaneously hypertensive rats through intervening the expression of TRPC3

International Journal of Cardiology ◽

10.1016/j.ijcard.2011.08.641 ◽

2011 ◽

Vol 152 ◽

pp. S53

Author(s):

Dongmei Yu ◽

Ming Chen

Keyword(s):

Left Ventricle ◽

Spontaneously Hypertensive Rats ◽

Cardiac Fibrosis ◽

Hypertensive Rats ◽

Spontaneously Hypertensive

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Physical Training as a Blood Pressure Reducer and a Remodeler of Cardiac Fibers in Spontaneously Hypertensive Rats (SHR)

Cardiology and Angiology An International Journal ◽

10.9734/ca/2021/v10i430175 ◽

2021 ◽

pp. 22-30

Author(s):

Mariana Molinar Mauad Cintra ◽

Matheus Ribeiro Bizuti ◽

Octávio Barbosa Neto ◽

Marlene Antônia dos Reis ◽

Lenaldo Branco Rocha ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Physical Training ◽

Spontaneously Hypertensive Rats ◽

Cardiac Fibrosis ◽

Left Ventricular ◽

Type Iii Collagen ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Type Iii

Background: Hypertension is the most prevalent of all cardiovascular diseases, reaching target organs such as the heart. Blood pressure control is critical for preventing organ damage induced by hypertension. Objective: To analyze blood pressure, heart rate, left ventricular thickness, the percentage of cardiac fibrosis and the percentage of type III collagen in Spontaneously Hypertensive Rats (SHR) submitted to swimming physical training. Methods: The experimental groups were composed of male Wistar Kyoto (WKY) rats (309-311g), which were divided into: 1) Normotensive Sedentary group (SN) (n = 6); 2) Trained Normotensive group (TN) (n = 6); 3) Sedentary Hypertensive group (SH) (n = 6); 4) Trained Hypertensive group (TH) (n = 6). After the end of the protocol, the animals were initially anesthetized to measure blood pressure. Results: Physical training was responsible for decreasing blood pressure (F = 16,968; p <0.001) and heart rate (F = 10.710; p = 0.004) in the trained groups (normotensive and hypertensive). Moreover, training was responsible for providing an increase in the thickness of the left ventricle (F = 7,254; p = 0.014) and a reduction in the percentage of cardiac fibrosis (F = 16,081; p <0.001). Furthermore, it was observed that the trained group had lower values of type III collagen (F = 13,166; p = 0.002). Conclusions: Physical swimming training triggered a decrease in blood pressure, heart rate, the percentage of fibrosis and the percentage of type III collagen. In addition, there was also a cardiac remodeling due to the increase in left ventricular hypertrophy.

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Sex-specific differences in age-dependent progression of aortic dysfunction and related cardiac remodeling in spontaneously hypertensive rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00231.2016 ◽

2017 ◽

Vol 312 (5) ◽

pp. R835-R849 ◽

Cited By ~ 8

Author(s):

Suzan Al-Gburi ◽

Andreas J. Deussen ◽

Roberta Galli ◽

Michael H. Muders ◽

Birgit Zatschler ◽

...

Keyword(s):

Arterial Pressure ◽

Cardiac Remodeling ◽

Spontaneously Hypertensive Rats ◽

Cardiac Fibrosis ◽

Renin Angiotensin System ◽

Left Ventricular ◽

Matrix Metalloproteinase 2 ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Functional Changes

Evidence of sex-specific differences in renin-angiotensin-system (RAS) and arterial pressure has been shown in many mammals, including spontaneously hypertensive rats (SHRs). Although SHRs have been used extensively as a leading experimental model of hypertension, the effects of sex-specific differences in RAS on aortic function and related cardiac remodeling during aging and hypertension have not been documented in detail. We examined structural and functional changes in aorta and heart of female and male SHRs at the ages of 5, 14, 29, and 36 wk. SHRs of both sexes were hypertensive from 14 wk. Aortic endothelial dysfunction and fibrosis, left ventricular (LV) hypertrophy, and cardiac fibrosis were evident at the age of 29 wk in male SHRs but first appeared only at the age of 36 wk in female SHRs. There was a pronounced delay of matrix metalloproteinase-2 activity in the aorta and heart of female SHRs, which was associated with preservation of 40% more elastin and less extensive cardiac fibrosis than in males. At 5, 29, and 36 wk of age, female SHRs showed higher levels of aortic and myocardial AT2R and MasR mRNA and decreased ANG II-mediated aortic constriction. Although female SHRs had increased relaxation to AT2R stimulation at 5 and 29 wk compared with males, this difference disappeared at 36 wk of age. This study documents sex-specific differences in the temporal progression of aortic dysfunction and LV hypertrophy in SHRs, which are independent of arterial pressure and are apparently mediated by higher AT2R expression in the heart and aorta of female SHRs.

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