DOSE-DEPENDENT EFFECTS OF PERINDOPRIL ON BLOOD-PRESSURE AND SMALL-ARTERY STRUCTURE

Long-term treatment of young spontaneously hypertensive rats (SHR) wit h angiotensin-converting enzyme (ACE) inhibitors has a persistent effe ct on blood pressure when treatment is withdrawn. The aim of the prese nt study was to determine whether this effect could be mediated by the effect of treatment on resistance-artery structure. We determined the dose dependence of ACE-inhibitor therapy on blood pressure and small- artery structure during treatment and on the recovery of blood pressur e when treatment was withdrawn. SHR (40 per group) were treated from a ge 4 to 24 weeks with one of three doses of perindopril (0.4, 0.8, or 1.5 mg/kg per day). Control groups were untreated SHR and Wistar-Kyoto rats. At 24 weeks, treatment was stopped and small arteries were take n from half of the rats from the mesenteric, femoral, cerebral, and co ronary vascular beds for morphological and functional measurements. Th e blood pressure of the other half of the rats was followed until 36 w eeks of age. During treatment, perindopril caused a dose-dependent red uction in blood pressure and in the media-lumen ratio and media area o f the small arteries, whereas there was a dose-dependent increase in l umen diameter. The effect of treatment on the structure of arteries fr om the different vascular beds was homogeneous. Compared with values f rom Wistar-Kyoto rats, blood pressure normalization in SHR was not ass ociated with full normalization of structure. After withdrawal of trea tment, there was an inverse relation between perindopril dose and the persistent effect. The results suggest that although treatment of SHR has a uniform effect on the structure of small arteries, this effect i s not directly related to the persistent effect on blood pressure when treatment is withdrawn.