Cardiovascular end-organ damage in Ren-2 transgenic rats compared to spontaneously hypertensive rats

Abstract

To compare hypertensive end-organ damage in two genetic forms of hypertension we assessed cardiovascular function in two rat strains of genetic hypertension: transgenic rats overexpressing the mouse Ren-2 gene [(TGR(mREN2)27]) and blood pressure matched spontaneously hypertensive rats (SHR). Despite similarly elevated blood pressure, systolic dp/dt (mmHg/s) was more impaired in transgenic rats (3099 +/- 446) than in SHR (3571 +/- 272) and normals (4342 +/- 119; P < 0.05). Left ventricular weight (mg/g body weight) increased more in the transgenic rats (40 +/- 3) than in SHR (31 +/- 2) and normals (26 +/- 2). Endothelium-dependent relaxation was significantly decreased only in the transgenic rats. This study shows significantly more cardiac and endothelial dysfunction in transgenic, hypertensive TGR (mREN2)27 than in age and blood pressure matched SHR. This supports the hypothesis that chronic activation of the renin-angiotensin system significantly contributes to hypertensive end-organ damage.

Cardiac Endothelin System Impairs Left Ventricular Function in Renin-Dependent Hypertension via Decreased Sarcoplasmic Reticulum Ca 2+ Uptake

“…12 An altered composition of the extracellular matrix has also been reported in the Ren2 model. 5,13 Our investigation using histological analysis with Sirius red staining revealed no alteration in interstitial fibrosis but an increased perivascular fibrosis in young Ren2-10 rats compared with SD-10 control rats. This finding is in agreement with previous observations in 16-week-old Ren2 rats.…”

“…5 The introduction of the mouse Ren2 gene (mRen2) led to a genetic model of renindependent hypertension, in which increased levels of cardiac angiotensin II have been described. 6 As a result, an important part of the cardiac pathophysiology has been ascribed to activation of the cardiac renin-angiotensin system.…”

Transgenic rats as models for hypertension

“…Systolic BP (SBP) in the TGR(hREN) rat heart. 18 This suggests that the activated extrarenal was normal. Confirming the species specificity of RAS might be responsible for the hypertensive the human renin.…”

“…18 That harbours the human angiotensinogen gene. The these pathophysiological changes are due to ANG II plasma levels of human angiotensinogen were is emphasised by the treatment with antihypertenextremely elevated in the TGR(hAOGEN) compared sive drugs.…”

Exercise training prevents development of cardiac contractile dysfunction in hypertensive TG(mREN2)27 rats

“…Both systolic and diastolic rates of pressure change (dP/dT) are reduced in 13-wk old Ren-2 rats when compared to age-matched, control Sprague Dawley(SD) rats (14). Maladaptation, characterized by re-expression of the fetal gene program and cardiac fibrosis, is commonly associated in left ventricular cardiac dysfunction (8;9;15).…”