Spontaneously hypertensive rats (SHR) are an established animal model for antihypertensive treatment. The aim of this pilot study was a systematic search for two lines of antihypertensive treatment – a monotherapy and a combination of two drugs – to be applied in a future study on old SHR. Originally, representatives of three drug classes recommended for antihypertensive therapy in humans should be applied, namely captopril (CAP) as an antagonist of the renin-angiotensin-aldosterone system, nifedipine (NIF) as calcium channel blocker and propranolol (PROP) as β-adrenergic blocker. As we observed that PROP had been poorly ingested, all groups with PROP therapy were excluded from the study. CAP (60 mg kg −1 d -1 ), NIF (10 mg kg −1 d -1 ) or both were administered orally to seven-week-old SHR over 3 weeks. A further group of SHR received no treatment (SHR/CTRL). Age-matched normotensive Wistar-Kyoto rats served as normotensive controls. We examined the effect of the antihypertensive therapies on systolic blood pressure, heart weight and on histological and biochemical markers of cardiac hypertrophy and fibrosis. CAP proved to be the most effective treatment reducing blood pressure and relative heart weight significantly compared to SHR/CTRL without reaching normotensive values. Beginning cardiac fibrosis observed in SHR/CTRL was completely abrogated with CAP treatment. Similar effects were achieved with a combination of CAP and NIF. CAP as monotherapy and CAP + NIF as combination therapy were chosen for the forthcoming study on old SHR.

Background: A major problem in the treatment of human hypertension is the late diagnosis of hypertension and, hence, the delayed start of treatment. Very often, hypertension has existed for a long time and cardiac damage has already developed. Therefore, we tested whether late-onset antihypertensive treatment is effective in lowering blood pressure (BP) and in reducing or even preventing left ventricular hypertrophy and fibrosis. Methods: Twenty-one male 60-week-old spontaneously hypertensive rats (SHR) were included. Fourteen rats received oral treatment with captopril (CAP) either as monotherapy or combined with nifedipine (CAP + NIF) over 22 weeks. Seven untreated SHR served as controls. We examined the therapeutic effects on BP, heart weight and histological and biochemical markers of left ventricular remodeling and fibrosis. Results: At 82 weeks of age, BP was reduced in the CAP and CAP + NIF groups by 44 and 51 mmHg, respectively (p < 0.001), but not in untreated controls. Despite the late therapy start, cardiac hypertrophy and fibrosis were attenuated compared to controls. Both treatments reduced heart weight by 1.2 mg/g (25%, p = 0.001) and collagens I and III by 66% and 60%, respectively (p < 0.001), thus proving nearly equivalent cardioprotective efficacy. Conclusion: These data clearly emphasize the benefit of antihypertensive treatment in reducing BP and mitigating the development of cardiac damage even when treatment is started late in life.

Numerous studies on the effects of antihypertensive treatment in young spontaneously hypertensive rats (SHRs) have shown that early-onset therapy may effectively reduce their blood pressure (BP) even to normotensive values. In contrast, only a few studies investigated the effects of treatment started at an advanced age. These studies revealed that antihypertensive effects are lower in adult or even in senescent SHRs compared with young SHRs. Even more, prevention of cardiac sequelae of hypertension such as hypertrophy and fibrosis is less effective when treatment starts late in life. Because, in patients, combination therapies with calcium antagonists are favored, we studied the efficacy of a combination therapy with captopril and nifedipine in young and old SHRs. We directly compared the treatment effects on BP as well as on cardiac hypertrophy and remodeling between these two animal cohorts. With antihypertensive treatment, significantly lower BP values were achieved in young SHRs despite a shorter treatment period compared with old SHRs. Although treatment effects on cardiac hypertrophy were greater in old than in young SHRs, cardiac fibrosis was significantly attenuated only in young but not in old SHRs. The results emphasize the value of antihypertensive therapy and particularly accentuate the importance of an early-onset therapy. With respect to problems such as late diagnosis and poor therapy adherence, these results may have great importance for the treatment of human hypertension.