08 Nov Left Ventricular Hypertrophy and preclinical Heart Failure in rodents
Left ventricular hypertrophy (LVH) is an enlargement and thickening of the walls of the heart’s main pumping chamber, the left ventricle. This condition can develop in response to some factors, such as high blood pressure or a heart condition, that causes the left ventricle to work harder. As the workload increases, the muscle tissue in the chamber wall thickens, and sometimes the size of the chamber itself also increases. The enlarged heart muscle loses elasticity and eventually may fail to pump with as much force as needed. LVH is a prognostic indicator of progression towards preclinical heart failure.
Pharmacological treatment of prehypertension, such as losarten, may in some cases ameliorate hypertension and improve vascular structure and function, which in turn may lead to a long‑term inhibition of the development of left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs). However, the underlying mechanism has yet to be fully elucidated.
The spontaneously hypertensive rat is an animal model that experiences or primary hypertension, and is used to study cardiovascular disease. It is the most studied model of hypertension measured as number of publications. The SHR strain was obtained during the 1960s by Okamoto and colleagues, who started breeding Wistar-Kyoto rats with high blood pressure.
Researchers looked into the expression of angiotensin type 1 receptor-associated protein (ATRAP/Agtrap), involved in vasoconstriction and the methylation of the Agtrap gene in the myocardium following the withdrawal of treatment. Spontaneously hypertensive rats were either treated with a saline solution, amlodipine, an oral drug that’s used to treat high blood pressure, or losartan for 6 weeks, and were compared to Wistar Kyoto rats (WKYs) as controls. Systolic blood pressure (SBP), left ventricular mass/body weight (LVM/BW), and cardiac fibrosis and structure were measured.
Only in prehypertensive losartan‑treated SHRs were reduced levels of SBP, LVM/BW, cardiac fibrosis and interventricular septum thickness maintained up to 32 weeks after the treatment was stopped. Moreover, an increased expression of ATRAP accompanied by the hypomethylation of the Agtrap promoter in the myocardium, was also only visible in the losartan‑treated SHRs, after treatment had stopped. This suggests that the hypomethylation of Agtrap with the upregulation of ATRAP are associated with the long‑term inhibition of LVH in SHRs with prehypertensive losartan treatment.
Syncrosome, a scientific preclinical CRO based in France, studies conditions linked to heart failure and arterial hypertension. They use spontaneously hypertensive rats for pharmacological inductions or research studies. They can monitor their Blood Pressure (Diastolic, Systolic, Mean) and heart rate using telemetry or classical catheter or Doppler echocardiography for example.. By combining all these parameters, they can most reliably test for appropriate reaction.
Key words: preclinical CRO, preclinical study, animal model, animal research, myocardial, ischemia, infarction, reperfusion, heart, rat model, mouse model, inflammation,preclinical heart failure, heart disease, losartan treatment, spontaneously hypertensive rat, Left ventricular hypertrophy