We investigated the development of cardiac changes in aged spontaneously hypertensive rats (SHR) with and without antihypertensive therapy. The objective of the study was to demonstrate development of cardiac hypertrophy and dilatation in untreated SHR and to investigate the effects of antihypertensive therapy in preventing these changes. Twenty-one SHR aged 60.5 +/­ 0.25 weeks were subdivided into a control group (C) and two groups receiving antihypertensive therapy with captopril (CAP) or with captopril plus nifedipin (C+N). Rats were observed over a period of 22 weeks with regular control of systolic blood pressure and echocardiographic data. After this period, organs and body fluids were obtained for histological and biochemical analyses.

We determined mRNA expression of atrial natriuretic peptide (ANP) and of collagen type I (coll I) and III (coll III) in the left ventricle (LV). Antihypertensive therapy significantly reduced mRNA indicating prevention of LV hypertrophy and fibrosis (CAP: ANP 0.26 +/­ 0.05, coll I 0.32 +/­ 0.04, coll III 0.38 +/­ 0.05; C+N: ANP 0.19 +/­ 0.05, coll I 0.26 +/­ 0.05, coll III 0.37 +/­ 0.06; values are % of untreated controls). Correspondingly, the development of echocardiographic data showed a significant loss of LV function in untreated SHR that was prevented by combination therapy with C+N. With CAP, improvement of pumping function was not significant. These results demonstrate that even a late-onset antihypertensive treatment can reduce cardiac remodelling and insufficiency resulting from hypertension.