Long-term hypotensive effects of an angiotensin converting enzyme inhibitor in spontaneously hypertensive rats: is there a role for vascular structure?
Male spontaneously hypertensive rats (SHR) were treated from 4 to 24 weeks of age with perindopril, an angiotensin converting enzyme (ACE) inhibitor, in doses of 0.4 and 0.8 mg/kg per day; we investigated the effects of these doses on blood pressure during and after withdrawal of treatment, and on the structural and functional characteristics of the resistance vessels. During treatment, mean blood pressure was maintained close to the level of normotensive control Wistar-Kyoto rats (WKY). At the age of 24 weeks, a resistance vessel segment was taken as a biopsy from the third branch of the superior mesenteric artery, and the structural and functional parameters were determined using an isometric myograph. Taken together with previous results the measurements showed that perindopril had a dose-dependent effect on both blood pressure and resistance vessel media thickness. Treatment was then withdrawn. Twelve weeks later, the mean blood pressure in both groups was still significantly reduced compared to that of age-matched SHR controls, but was no longer dose-related, nor was it related to the resistance vessel media thickness at age 24 weeks. The results suggest that the continuing reduction in blood pressure after withdrawal of treatment with perindopril may not be directly related to the drug's effect on resistance vessel structure.
Christensen
H R
HR
Institutes of Biophysics and Pathology, Aarhus University, Denmark.
Nielsen
H
H
Christensen
K L
KL
Baandrup
U
U
Jespersen
L T
LT
Mulvany
M J
MJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D066298:In Vitro Techniques; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D020913:Perindopril