*Article* **How Do Young and Old Spontaneously Hypertensive Rats Respond to Antihypertensive Therapy? Comparative Studies on the Effects of Combined Captopril and Nifedipine Treatment**

**Beate Rassler \*, Christina Hawlitschek, Julia Brendel and Heinz-Gerd Zimmer**

Carl-Ludwig-Institute of Physiology, University of Leipzig, 04103 Leipzig, Germany **\*** Correspondence: beate.rassler@medizin.uni-leipzig.de; Tel.: +49-341-9715565

**Abstract:** 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.

**Keywords:** young SHR; old SHR; antihypertensive therapy; combination therapy; treatment effect; systolic blood pressure; LV hypertrophy; cardiac fibrosis
