Dose-dependent effects of perindopril on blood pressure and small-artery structure.
Long-term treatment of young spontaneously hypertensive rats (SHR) with angiotensin-converting enzyme (ACE) inhibitors has a persistent effect on blood pressure when treatment is withdrawn. The aim of the present 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on blood pressure and small-artery structure during treatment and on the recovery of blood pressure when treatment was withdrawn. SHR (40 per group) were treated from age 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 taken from half of the rats from the mesenteric, femoral, cerebral, and coronary vascular beds for morphological and functional measurements. The blood pressure of the other half of the rats was followed until 36 weeks of age. During treatment, perindopril caused a dose-dependent reduction in blood pressure and in the media-lumen ratio and media area of the small arteries, whereas there was a dose-dependent increase in lumen diameter. The effect of treatment on the structure of arteries from the different vascular beds was homogeneous. Compared with values from Wistar-Kyoto rats, blood pressure normalization in SHR was not associated with full normalization of structure. After withdrawal of treatment, there was an inverse relation between perindopril dose and the persistent effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Thybo
N K
NK
Department of Pharmacology, University of Aarhus, Denmark.
Korsgaard
N
N
Eriksen
S
S
Christensen
K L
KL
Mulvany
M J
MJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects* / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; D020913:Perindopril